EP4379067B1

EP4379067B1 - Iridoid derivatives and their use in a tanning process

Info

Publication number: EP4379067B1
Application number: EP22306769.5A
Authority: EP
Inventors: Loic FONTAINE; Thomas Lecourt; Alexandra Le Foll; Stéphane MARCOTTE
Original assignee: Centre National de la Recherche Scientifique CNRS; Universite de Rouen; Hermes Sellier SAS; Institut National des Sciences Appliquees de Rouen
Current assignee: Centre National de la Recherche Scientifique CNRS; Universite de Rouen; Hermes Sellier SAS; Institut National des Sciences Appliquees de Rouen
Priority date: 2022-12-01
Filing date: 2022-12-01
Publication date: 2026-02-11
Anticipated expiration: 2042-12-01
Also published as: EP4379067A1

Description

TECHNICAL FIELD

The present invention relates to the field of tanning. More particularly, the present invention relates to particular iridoid derivatives and their use in a tanning process. It also relates to a process for cross-linking collagen using such iridoid derivatives. The invention is set out in the appended set of claims.

TECHNICAL BACKGROUND

Natural tannins have long been used in processes for tanning hides and stabilizing collagen. Tanning mixtures are mainly composed of polyphenolic tannins, which are divided into two classes: condensed tannins and hydrolysable tannins. The effectiveness of tanning is usually reflected by its ability to stabilize collagen, namely to limit collagen denaturation and impart good resistance to enzymatic hydrolysis. Collagen stabilization can be assessed by measuring the increase in shrinkage temperature, which is correlated to the collagen denaturation temperature. The polyphenolic tannins give rise to a shrinkage temperature around 75-85°C. Other parameters can also be considered for assessing the effectiveness of tanning, such as the mechanical resistance of the hide and its sensory parameters, such as hide filling and suppleness.
However, due to their astringency, natural polyphenolic tannins lead to a tension of the hide. In order to limit such tension, a pre-tanning step using a metal salt, such as aluminum, iron, zirconium, titanium, or chromium, or synthetic tannins, such as glutaraldehyde or oxazolidine, is usually required.
Recently, a new class of natural tanning or pre-tanning agents has been identified: these are iridoids and seco-iridoids. Among these compounds, genipin can be obtained from the fruit of Gardenia jasminoides or Genipa americana. Genipin allows to stabilize collagen and to reach shrinkage temperatures of 80°C (Zhang et al., JALCA, 2011, 106, 121). Genipin has also been used in combination with an aluminum-based tanning (Ding et al., JALCA, 2008, 103, 377), which resulted in a soft and full leather having a shrinkage temperature of 92°C. Genipin has also been used to cross-link gelatin (Taylor et al., JALCA, 2009, 104, 79). Genipin is readily available in large quantities and is a known food coloring agent. However, using genepin in a tanning process leads to a dark blue color, which can be undesirable.
Other natural iridoids have been used in processes for tanning or pre-tanning hides. In particular, WO2009/065915 describes a tanning method using aglycone derivatives of iridoids and seco-iridoids, different from genipin. Such derivatives, which can be extracted from olive leaves, are hydrolyzed forms and aglycone forms of oleuropein. The mixture obtained by extraction of the leaves in the presence of endogenous enzyme or by the use of acid is not purified and comprises polyphenolic compounds and compounds derived from hydrolyzed oleuropein, such as (4E)-4-formyl-3-(-1-formyl-2-methoxy-2-oxoethyl)hex-4-enoic acid. Schröpfer and Meyer (IULTCS Congress Dresden, 2019) also describe using a powder of dry leaves of Ligustrum vulgare or an extract thereof, in a process for tanning hides. The extracts contain iridoids of the oleuropein and ligustaloside A and B. Leathers having shrinkage temperatures between 80 and 85°C and having a light beige to brown color are obtained. However, in such methods, the low amounts of active agents in the tanning mixture imply that a large amount of such mixture must be used to obtain sufficient tanning activity. This leads to a high organic content in tanneries effluent that need to be costly treated by waste water-treatments. In addition, the extracts have a low purity and can contain co-extracted molecules, which usually cause coloring issues.
Document US 2017/080040-A1 discloses a decoction of olive leaves which can be used in the treatment of tanning hides and which comprises an aqueous composition containing at least from about 500 mg/L to about 3,000 mg/L of oleuropein, from about 100 mg/L to about 300 mg/L of hydroxytyrosol, from about 90 mg/L to about 280 mg/L of tyrosol, from about 400 mg/L to about 1,800 mg/L of elenolic acid.
Therefore, there remains a need to provide effective pre-tanning or tanning agents that overcome the aforementioned limitations.

SUMMARY OF THE INVENTION

In this respect, the inventors have demonstrated that particular derivatives of the genipin could be easily prepared in few steps, and used in a tanning process. The inventors have shown that such tanning agents were at least as effective as genipin, but advantageously, did not lead to a dark color of the hide. The derivatives can be produced in high amounts starting from genipin, and their high purity allows to use low amounts of tanning mixture.
Thus, the present invention relates to the use of a compound represented by the following formula (I), in a tanning process: wherein:

R₁ is a hydrogen atom, a C₁-C₁₂ aliphatic group, aryl, -C(O)-(C₁-C₁₂ aliphatic group), -C(O)-(aryl), -CH₂-O-(C₁-C₁₂ aliphatic group), or -CH₂-O-(aryl), said aliphatic groups being each independently optionally substituted by an aryl, a halide, -OH, -O-(C₁-C₁₂ aliphatic group), - N(C₁-C₁₂ aliphatic group)(C₁-C₁₂ aliphatic group), -O-C(O)-(C₁-C₁₂ aliphatic group), -C(O)-O-(C₁-C₁₂ aliphatic group), -C(O)-NH-(C₁-C₁₂ aliphatic group), -NH-C(O)-(C₁-C₁₂ aliphatic group), -NH-C(O)-NH-(C₁-C₁₂ aliphatic group), -NH-C(O)-O-(C₁-C₁₂ aliphatic group), -O-C(O)-NH-(C₁-C₁₂ aliphatic group), or -O-C(O)-O-(C₁-C₁₂ aliphatic group),
R₂ is a hydrogen atom or a (C₁-C₁₂) aliphatic group,
R₃ is -CH₂-C(O)H or -CH₂-CH₂-OH,
R₄ is -C(O)-CH₂-R₅ or -CH(OH)-CH₂-R₅', where R₅ and R₅' are each independently a hydrogen atom, a C₁-C₁₂ aliphatic group, -OH, or -O-C(O)-(C₁-C₁₂ aliphatic group),

₃

₄

₆

₇

₈

₉

₁

₁₂

In some embodiments, R₁ is a hydrogen atom or -C(O)-(C₁-C₁₂ aliphatic group), preferably a hydrogen atom or -C(O)-(C₁-C₆ alkyl).
In some embodiments, R₂ is a C₁-C₁₂ aliphatic group, preferably a C₁-C₆ alkyl.
In some embodiments, R₄ is -C(O)-CH₂-R₅, where R₅ is a hydrogen atom or -O-C(O)-(C₁-C₁₂ aliphatic group), preferably a hydrogen atom or -O-C(O)-(C₁-C₆ alkyl).
In some embodiments, R₆ is hydrogen.
In some embodiments, R₇ is -OH or -O-C(O)-(C₁-C₁₂ aliphatic group), preferably -OH or -O-C(O)-(C₁-C₆ alkyl).
In some embodiments, R₈ is -OH.
In some embodiments, R₉ is a hydrogen atom or -O-C(O)-(C₁-C₆ alkyl).
In a preferred embodiment, said compound of formula (I) is one of the following compounds:
In another preferred embodiment, said compound of formula (I) is one of the following compounds:
In a particular embodiment, a use according to the invention is a use for tanning a hide or a skin.
In another particular embodiment, a use according to the invention is a use in a method for manufacturing a leather or a leather substitute.
In a further particular embodiment, a use according to the invention is a use for tanning a collagen-containing material.
The present invention also relates to a compound of formula (I) per se, as defined herein, with the proviso that the compound is not one of the following compounds:
Another object of the present invention is a process for cross-linking collagen in a material comprising a step of contacting said material with a compound of formula (I) as defined herein. In a particular embodiment, said material is a hide or skin.

FIGURES

Figure 1: Images of materials obtained after tanning of a collagen powder using compounds of the invention (compounds 3a, 3b, 4, 6, 7, and 8) and comparative compounds (compounds 2 and 5).
Figure 2: Image of a material obtained after tanning of a calf hide using compounds 3a and 3b.

DETAILED DESCRIPTION OF THE INVENTION

Definitions

The expression "C_x-C_y" in which x and y are integers, as used in the present disclosure, means that the corresponding chemical group comprises from x to y carbon atoms. If, for example, the expression C₁-C₆ is used, it means that the corresponding chemical group may comprise from 1 to 6 carbon atoms, especially 1, 2, 3, 4, 5 or 6 carbon atoms. If, for example, the expression C₂-C₅ is used, it means that the corresponding chemical group may comprise from 2 to 5 carbon atoms, especially 2, 3, 4, or 5 carbon atoms.
The term "aliphatic" refers to a non-aromatic, saturated or unsaturated, cyclic or acyclic (preferably acyclic), linear or branched hydrocarbon chain. The expression "C₁-C₁₂ aliphatic" refers to an aliphatic having 1 to 12 carbon atoms. In particular, the aliphatic may be an alkyl, an alkenyl, or an alkynyl.
The term "alkyl" refers to a saturated, acyclic, linear or branched hydrocarbon chain. The expression "C₁-C₆ alkyl" refers to an alkyl having 1 to 6 carbon atoms. Examples of alkyl (or C₁-C₆ alkyl) include, for instance, methyl, ethyl, propyl, isopropyl, butyl, isobutyl, tert-butyl, pentyl, or hexyl.
The term "alkenyl" refers to an unsaturated, acyclic, linear or branched hydrocarbon chain, having at least one carbon-carbon double bond. The expression "C₂-C₆ alkenyl" refers to an alkenyl having 2 to 6 carbon atoms. Examples of alkenyl (or C₂-C₆ alkenyl) include for instance, ethenyl, propenyl, butenyl, pentenyl, or hexenyl.
The term "alkynyl" refers to an unsaturated, acyclic, linear or branched hydrocarbon chain, having at least one carbon-carbon triple bond. The expression "C₂-C₆ alkynyl" refers to an alkynyl having 2 to 6 carbon atoms. Examples of alkynyl (or C₂-C₆ alkynyl) include, for instance, ethynyl, propynyl, butynyl, pentynyl, or hexynyl.
The term "aryl" refers to a mono- or bi-cyclic aromatic hydrocarbon having from 6 to 12 carbon atoms. For instance, the term "aryl" includes phenyl, biphenyl, or naphthyl. In a preferred embodiment, the aryl is a phenyl.
The present invention relates to the use of a compound represented by the following formula (I), in a tanning process: wherein:

₃

₄

₆

₇

₈

₉

₁

₁₂

Compounds of formula (I) as represented herein include all possible stereoisomers, and include not only racemic compounds but also the optically active isomers as well. The term "stereoisomer" refers to compounds which have identical molecular formulae as identified herein but which differ in the layout of their atoms in space. Stereoisomers which are not mirror images of each other, are designated as "diastereoisomers", and stereoisomers which are non-superposable mirror images of each other are designated as "enantiomers" or "optical isomers". "Stereoisomers" refer to racemates, enantiomers and diastereoisomers.
In a particular embodiment, the compound of formula (I) as defined herein is a compound of formula (III), a compound of formula (IV), or a mixture thereof: wherein, in formulae (III) and (IV):

R₁, R₂, R₃ and R₄ are as defined in formula (I),
when R₄ is -C(O)-CH₂-R₅, then R₅ is as defined in formula (I),
when R₃ and R₄ form together said chain of formula (II), then R₆, R₇, R₈, and R₉ are as defined in formula (I).

Preferably, the compound of the invention is a compound of formula (III) or a mixture (in particular, a racemic mixture) of a compound of formula (III) and a compound of formula (IV). More preferably, the compound of the invention is a compound of formula (III).
The "salts" of the compounds of the invention include usual salts formed from inorganic or organic acids or bases as well as quaternary ammonium salts. More specific examples of suitable acid salts include hydrochloric, hydrobromic, sulfuric, phosphoric, nitric, perchloric, fumaric, acetic, propionic, succinic, glycolic, formic, lactic, maleic, tartaric, citric, palmoic, malonic, hydroxymaleic, phenylacetic, glutamic, benzoic, salicylic, fumaric, toluenesulfonic, methanesulfonic, naphthalene-2-sulfonic, benzenesulfonic hydroxynaphthoic, hydroiodic, malic, steroic, tannic etc. More specific examples of suitable basic salts include sodium, lithium, potassium, magnesium, aluminum, calcium, zinc salts.
R₁ is a hydrogen atom, a C₁-C₁₂ aliphatic group, aryl, -C(O)-(C₁-C₁₂ aliphatic group), -C(O)-(aryl), -CH₂-O-(C₁-C₁₂ aliphatic group), or -CH₂-O-(aryl), said aliphatic groups being each independently optionally substituted by an aryl, a halide, -OH, -O-(C₁-C₁₂ aliphatic group), - N(C₁-C₁₂ aliphatic group)(C₁-C₁₂ aliphatic group), -O-C(O)-(C₁-C₁₂ aliphatic group), -C(O)-O-(C₁-C₁₂ aliphatic group), -C(O)-NH-(C₁-C₁₂ aliphatic group), -NH-C(O)-(C₁-C₁₂ aliphatic group), -NH-C(O)-NH-(C₁-C₁₂ aliphatic group), -NH-C(O)-O-(C₁-C₁₂ aliphatic group), -O-C(O)-NH-(C₁-C₁₂ aliphatic group), or -O-C(O)-O-(C₁-C₁₂ aliphatic group). In other words, R₁ is:

a hydrogen atom,
a C₁-C₁₂ aliphatic group unsubstituted or substituted by an aryl, a halide, -OH, -O-(unsubstituted C₁-C₁₂ aliphatic group), -N(unsubstituted C₁-C₁₂ aliphatic group)(unsubstituted C₁-C₁₂ aliphatic group), -O-C(O)-(unsubstituted C₁-C₁₂ aliphatic group), -C(O)-O-(unsubstituted C₁-C₁₂ aliphatic group), -C(O)-NH-(unsubstituted C₁-C₁₂ aliphatic group), -NH-C(O)-(unsubstituted C₁-C₁₂ aliphatic group), -NH-C(O)-NH-(unsubstituted C₁-C₁₂ aliphatic group), -NH-C(O)-O-(unsubstituted C₁-C₁₂ aliphatic group), -O-C(O)-NH-(unsubstituted C₁-C₁₂ aliphatic group), or -O-C(O)-O-(unsubstituted C₁-C₁₂ aliphatic group),
an aryl,
-C(O)-(C₁-C₁₂ aliphatic group unsubstituted or substituted by an aryl, a halide, -OH, -O-(unsubstituted C₁-C₁₂ aliphatic group), -N(unsubstituted C₁-C₁₂ aliphatic group)(unsubstituted C₁-C₁₂ aliphatic group), -O-C(O)-(unsubstituted C₁-C₁₂ aliphatic group), -C(O)-O-(unsubstituted C₁-C₁₂ aliphatic group), -C(O)-NH-(unsubstituted C₁-C₁₂ aliphatic group), -NH-C(O)-(unsubstituted C₁-C₁₂ aliphatic group), -NH-C(O)-NH-(unsubstituted C₁-C₁₂ aliphatic group), -NH-C(O)-O-(unsubstituted C₁-C₁₂ aliphatic group), -O-C(O)-NH-(unsubstituted C₁-C₁₂ aliphatic group), or -O-C(O)-O-(unsubstituted C₁-C₁₂ aliphatic group)),
-C(O)-(aryl),
-CH₂-O-(C₁-C₁₂ aliphatic group unsubstituted or substituted by an aryl, a halide, -OH, -O-(unsubstituted C₁-C₁₂ aliphatic group), -N(unsubstituted C₁-C₁₂ aliphatic group)(unsubstituted C₁-C₁₂ aliphatic group), -O-C(O)-(unsubstituted C₁-C₁₂ aliphatic group), -C(O)-O-(unsubstituted C₁-C₁₂ aliphatic group), -C(O)-NH-(unsubstituted C₁-C₁₂ aliphatic group), -NH-C(O)-(unsubstituted C₁-C₁₂ aliphatic group), -NH-C(O)-NH-(unsubstituted C₁-C₁₂ aliphatic group), -NH-C(O)-O-(unsubstituted C₁-C₁₂ aliphatic group), -O-C(O)-NH-(unsubstituted C₁-C₁₂ aliphatic group), or -O-C(O)-O-(unsubstituted C₁-C₁₂ aliphatic group)), or
CH₂-O-(aryl).

Preferably, R₁ is a hydrogen atom, a C₁-C₁₂ aliphatic group, aryl, -C(O)-(C₁-C₁₂ aliphatic group), -C(O)-(aryl), -CH₂-O-(C₁-C₁₂ aliphatic group), or -CH₂-O-(aryl), said aliphatic groups being each independently optionally substituted by an aryl.
A preferred C₁-C₁₂ aliphatic group substituted by an aryl is a methyl substituted by a phenyl, namely a benzyl.
More preferably, R₁ is a hydrogen atom, a C₁-C₁₂ aliphatic group, aryl, -C(O)-(C₁-C₁₂ aliphatic group), -C(O)-(aryl), -CH₂-O-(C₁-C₁₂ aliphatic group), or -CH₂-O-(aryl), said aliphatic groups being each unsubstituted.
A preferred C₁-C₁₂ aliphatic group in R₁ is a C₁-C₆ alkyl.
In another particular embodiment, R₁ is a hydrogen atom, a C₁-C₁₂ aliphatic group, -C(O)-(C₁-C₁₂ aliphatic group), -CH₂-O-(C₁-C₁₂ aliphatic group), said aliphatic groups being each independently optionally substituted by an aryl. In a more particular embodiment, R₁ is a hydrogen atom or -C(O)-(C₁-C₁₂ aliphatic group).
In a more particular embodiment, R₁ is a hydrogen atom, a C₁-C₆ alkyl group, -C(O)-(C₁-C₆ alkyl), -CH₂-O-(C₁-C₆ alkyl group), said alkyl groups being each independently optionally substituted by phenyl.
Preferably, R₁ is a hydrogen atom or a -C(O)-(C₁-C₆ alkyl) such as -C(O)-CH₃.
More preferably, R₁ is -C(O)-(C₁-C₆ alkyl), such as -C(O)-CH₃.
R₂ is a hydrogen atom or a C₁-C₁₂ aliphatic group. More particularly, R₂ may be a hydrogen atom or a C₁-C₆ alkyl group.
Preferably, R₂ is a C₁-C₁₂ aliphatic group, more preferably a C₁-C₆ alkyl, such as a methyl.
In a preferred embodiment, the compound of formula (I) is such that:

R₁ is a hydrogen atom or -C(O)-(C₁-C₆ alkyl); and
R₂ is a C₁-C₆ alkyl group.

In a particular embodiment, the compound of formula (I) is such that:

R₃ is -CH₂-C(O)H or -CH₂-CH₂-OH (preferably -CH₂-C(O)H); and
R₄ is -C(O)-CH₂-R₅ or -CH(OH)-CH₂-R₅', where R₅ and R₅' are each independently a hydrogen atom, a C₁-C₁₂ aliphatic group, -OH, or -O-C(O)-(C₁-C₁₂ aliphatic group). Preferably, R₄ is -C(O)-CH₂-R₅, where R₅ is as defined herein.

In particular, R₅ is a hydrogen atom, a C₁-C₆ alkyl group, -OH, or -O-C(O)-(C₁-C₆ alkyl group).
Preferably, R₅ is a hydrogen atom or -O-C(O)-(C₁-C₁₂ aliphatic group), more preferably a hydrogen atom or -O-C(O)-(C₁-C₆ alkyl), even more preferably, a hydrogen atom or -O-C(O)-CH₃.
In particular, R₅' is a hydrogen atom, a C₁-C₆ alkyl group, -OH, or -O-C(O)-(C₁-C₆ alkyl group). Preferably, R₅' is hydrogen atom, -OH, or -O-C(O)-CH₃. More preferably, R₅' is -OH.
In a preferred embodiment, the compound of formula (I) is such that:

R₃ is -CH₂-C(O)H; and
R₄ is -C(O)-CH₂-R₅, where R₅ is a hydrogen atom or -O-C(O)-(C₁-C₆ alkyl) (such as -O-C(O)-CH₃).

In a more preferred embodiment, the compound of formula (I) is such that:

R₁ is a -C(O)-(C₁-C₆ alkyl);
R₂ is a C₁-C₆ alkyl group;
R₃ is -CH₂-C(O)H; and
R₄ is -C(O)-CH₂-R₅, where R₅ is a hydrogen atom or -O-C(O)-(C₁-C₆ alkyl) (such as -O-C(O)-CH₃).

In another particular embodiment, R₃ and R₄ form together a chain of formula (II) as defined herein, wherein R₆, R₇, R₈, and R₉ are each independently a hydrogen atom, -OH, or -O-C(O)-(C₁-C₁₂ aliphatic group). In such embodiment, the compound of formula (I) can be represented as follows: wherein R₁, R₂, R₆, R₇, R₈, and R₉ are as defined herein.
More particularly, the stereochemistry of the compound of formula (I-II) may be as follow: wherein R₁, R₂, R₆, R₇, R₈, and R₉ are as defined herein.
Preferably, the compound of the invention is a compound of formula (III-II) or a mixture (in particular, a racemic mixture) of a compound of formula (III-II) and a compound of formula (IV-II). More preferably, the compound of the invention is a compound of formula (III-II).
It is understood that, in any formula represented herein, such as formula (I), (II), (III), (IV), (I-II), (III-II) or (IV-II), each stereogenic center that is not defined encompasses both (R) and (S) configurations.
In a particular embodiment, R₆, R₇, R₈, and R₉ are each independently a hydrogen atom, -OH, or -O-C(O)-(C₁-C₆ alkyl group).
In a particular embodiment, at least one (preferably at least two) among R₇, R₈, and R₉ (for instance, all of R₇, R₈, and R₉) are not hydrogen atoms.
In a preferred embodiment, R₆ is hydrogen.
In a particular embodiment, R₇ is hydrogen, -OH or -O-C(O)-(C₁-C₆ alkyl), for instance hydrogen, -OH or -O-C(O)-CH₃.
In another particular embodiment, R₇ is -OH or -O-C(O)-(C₁-C₁₂ aliphatic group).
Preferably, R₇ is -OH or -O-C(O)-(C₁-C₆ alkyl), more preferably -OH or -O-C(O)-CH₃.
In another particular embodiment, R₇ is -O-C(O)-(C₁-C₁₂ aliphatic group), for instance -C(O)-CH₃.
In a particular embodiment, R₈ is hydrogen or -OH. Preferably, R₅ is -OH.
In a particular embodiment, R₉ is a hydrogen atom, -OH, or -O-C(O)-(C₁-C₆ alkyl), preferably a hydrogen atom, -OH or -O-C(O)-CH₃.
In a more particular embodiment, R₉ is a hydrogen atom or -O-C(O)-(C₁-C₁₂ aliphatic group). Preferably, R₉ is a hydrogen atom or -O-C(O)-(C₁-C₆ alkyl), more preferably a hydrogen atom or -O-C(O)-CH₃.
In another particular embodiment, R₉ is -O-C(O)-(C₁-C₁₂ aliphatic group), for instance -C(O)-CH₃.
In a particular embodiment, the compound of formula (I) (or of formula (I-II)) is such that R₃ and R₄ form together a chain of formula (II) wherein:

R₆ is hydrogen;
R₇ is hydrogen, -OH or -O-C(O)-(C₁-C₆ alkyl), preferably hydrogen, -OH or -O-C(O)-CH₃;
R₈ is hydrogen or -OH; and
R₉ is a hydrogen atom, -OH, or -O-C(O)-(C₁-C₆ alkyl), preferably a hydrogen atom, -OH, or
O-C(O)-CH₃.

In a more particular embodiment, the compound of formula (I) (or of formula (I-II)) is such that:

R₁ is a hydrogen atom or -C(O)-(C₁-C₆ alkyl);
R₂ is a C₁-C₆ alkyl group;
R₃ and R₄ form together a chain of formula (II) wherein:
- R₆ is hydrogen;
- R₇ is hydrogen, -OH or -O-C(O)-(C₁-C₆ alkyl), preferably hydrogen, -OH or - O-C(O)-CH₃;
- R₈ is hydrogen or -OH; and
- R₉ is a hydrogen atom, -OH, or -O-C(O)-(C₁-C₆ alkyl), preferably a hydrogen atom, -OH, or -O-C(O)-CH₃.

In a preferred embodiment, the compound of formula (I) (or of formula (I-II)) is such that R₃ and R₄ form together a chain of formula (II) wherein:

R₆ is hydrogen;
R₇ is OH or -O-C(O)-(C₁-C₆ alkyl), preferably -OH or -O-C(O)-CH₃;
R₈ is -OH; and
R₉ is a hydrogen atom or -O-C(O)-(C₁-C₆ alkyl), preferably a hydrogen atom or -O-C(O)-CH₃.

In a more preferred embodiment, the compound of formula (I) (or of formula (I-II)) is such that:

R₁ is a hydrogen atom or -C(O)-(C₁-C₆ alkyl);
R₂ is a C₁-C₆ alkyl group;
R₃ and R₄ form together a chain of formula (II) wherein:
- R₆ is hydrogen;
- R₇ is OH or -O-C(O)-(C₁-C₆ alkyl), preferably -OH or -O-C(O)-CH₃;
- R₈ is -OH; and
- R₉ is a hydrogen atom or -O-C(O)-(C₁-C₆ alkyl), preferably a hydrogen atom or -O-C(O)-CH₃.

In a preferred embodiment, the compound of formula (I) is one of the following compounds:
More preferably, the compound of formula (I) is one of the following compounds:
In another preferred embodiment, the compound of formula (I) used in the present invention is one of the following known compounds:
More preferably, the compound of formula (I) used in the present invention is one of the following compounds:
In a particular embodiment, the compound of formula (I) is not one of the following compounds (including any stereoisomer thereof):
Compounds of the invention can be prepared by any suitable technique known to the skilled artisan. In particular, compounds of the invention can be prepared as detailed in the examples. For instance, such compounds can be prepared starting from genipin, and by subjecting genipin to a succession of suitable synthetic reactions, such as oxidation, reduction, dihydroxylation, and/or acylation.
Compounds of formula (I) as defined herein are particularly suitable for use in a tanning process, as tanning or pre-tanning agents. The "pre-tanning" refers a particular step of a tanning process, which is a preliminary step where a first tanning agent (i.e. "pre-tanning agent") is contacted with the collagen-containing material, e.g. the hide, before being contacted with a second tanning agent (i.e. "tanning agent"). Advantageously, the pre-tanning also enables the shaving of the leather before the second tanning agent is applied.
A tanning process may comprise or not a pre-tanning step. The compound of formula (I) according to the invention may be used as a pre-tanning agent and/or tanning agent in a process comprising a pre-tanning step. In such embodiment, if one among the pre-tanning agent and the tanning agent is not a compound of formula (I), it may be chosen from the group consisting of: polyphenolic extract for various vegetable, mainly gallnut, quebracho, oak, metal salt of chromium, iron, zirconium, titanium, aluminum, mainly with chloride and sulfate as counter ion, and synthetics chemicals like formol, glutaraldehyde, oxazolidine, zeolite, formol phenol (and derivate like cresol, phenol sulfonic acids) condensate, formol bisphenol (A, B, S and F) condensate, formol melamine condensate, and a mixture thereof.
The compound of formula (I) according to the invention may be used as a tanning agent in a tanning process not comprising a pre-tanning step.
The tanning process may in particular be a process for tanning a collagen-containing material, and more particularly for tanning a hide or a skin.
In said tanning process, said collagen-containing material, or said hide or skin, is treated (typically, contacted) with one or more compounds of formula (I), or a composition comprising the same.
As used herein, the term "collagen" refers to naturally occurring collagens or modified collagens. The term "collagen" as used herein also refers to collagens prepared using recombinant techniques. The term collagen includes collagen, collagen fragments, collagen dispersion obtained from hide grinding and various purification steps (e.g. enzymatic or acidic hydrolysis), collagen fibers obtained through precipitation of dispersed or soluble collagen (e.g. salt, brine or ammoniac precipitation), collagen-like proteins, triple helical collagen, alpha chains, monomers, gelatin, trimers and combinations thereof. Recombinant expression of collagen and collagen-like proteins is known in the art (see in particular EP 1,232,182 ; US 6,428,978 ; US 8,188,230 ). In some embodiments, the collagen can be a chemically-modified collagen, a truncated collagen, unmodified or post-translationally modified, or amino acid sequence-modified collagen. In some embodiments, the collagen can be plant-based collagen. In some embodiments, a collagen solution can be fibrillated into collagen fibrils. As used herein, collagen fibrils refer to nanofibers composed of tropocollagen or tropocollagen-like structures. In some embodiments, a recombinant collagen can comprise a collagen fragment of the amino acid sequence of a native collagen molecule capable of forming tropocollagen (trimeric collagen). A recombinant collagen can also comprise a modified collagen or truncated collagen having an amino acid sequence at least 70, 80, 90, 95, 96, 97, 98, or 99% identical or similar to a native collagen amino acid sequence. In some embodiments, the collagen fragment can be a 50 kDa portion of a native collagen. Methods of producing recombinant collagen and recombinant collagen fragments are known in the art. (see in particular US 2019/0002893 , US 2019/0040400 , US 2019/0093116 , and US 2019/0092838 ).
The collagen-containing material refers to a material comprising or consisting of collagen. The collagen-containing material may be from any origin, in particular from an animal (e.g. goat, bovine such as calf, cow or cattle, ovine such as sheep or lamb, reptile such as crocodile or lizard, or fish such as trout or salmon). In a particular embodiment, said collagen-containing material is a hide or a skin. The hide or skin may be from any animal, (e.g. goat, bovine such as calf, cow or cattle, ovine such as sheep or lamb, reptile such as crocodile or lizard, or fish such as trout or salmon).
The treating or contacting step may be carried out under classical conditions known to the skilled artisan. For instance, the collagen-containing material (in particular, said hide or skin) may be contacted with said one or more compounds of formula (I) in an aqueous solution, optionally comprising further auxiliary agents such as, proteins, peptides, protein hydrosylates, polyamines, pH buffer, sodium chloride, sodium sulfate, sodium citrate, ammonium chloride, naphthalene sulfonic polymer, preservatives, or slippery agent. The concentration of compound(s) of formula (I) in the aqueous solution is typically comprised between 0.1 wt% and 40 wt%, preferably between 0.5% and 25%. The pH of the aqueous solution may be within a range from 1 to 15, preferably from 7 to 11. Said pH may be adjusted by using a buffer, such as a carbonate or phosphate buffer. The treating or contacting step may be carried out at a temperature comprised between 4 °C and 70 °C, preferably between 20 °C and 50 °C, more preferably between 30 °C and 40 °C. The treating or contacting step may be carried out for a duration comprised between 1 hour and 90 hours, preferably between 15 hours and 50 hours. In some embodiments, the compound(s) of formula (I) may be used in a tanning process in combination with other tanning agents, such as mineral, vegetal, organic or enzymatic tanning agents (e.g. polyphenolic extract for various vegetable, mainly gallnut, quebracho, oak, metal salt of chromium, iron, zirconium, titanium, aluminum, mainly with chloride and sulfate as counter ion, and synthetics chemicals like formol, glutaraldehyde, oxazolidine, zeolite, formol phenol (and derivate like cresol, phenol sulfonic acids) condensate, formol bisphenol (A, B, S and F) condensate, formol melamine condensate, and a mixture thereof). The tanning step can be carried out in a tanning drum, a reactor or any other adapted device.
Advantageously, compounds of formula (I) used according to the invention allow to obtain a high-quality leather or leather substitute. In particular, said leather or leather substitute may:

be colorless or slightly colored (for instance, yellow, orange, beige), and/or
have a shrinkage temperature of at least 65°C (for instance from 65°C to 90°C), or at least 70 °C (for instance, from 70°C to 85°C), as measured by DSC, and/or
have a high-quality grain and leather surface.

The shrinkage temperature may in particular be suitable to shave leather and to prepare the step of tanning (i.e. the step subsequent to the pre-tanning, if present in the tanning process). The high-quality grain and leather surface may in particular be suitable for aniline finishing, and be characterized by a very low shrinking of the grain.
Hence, in a particular embodiment, compounds of formula (I) are used in a method for manufacturing a leather or leather substitute. A "leather substitute" refers typically to a material having similar properties as leather, and obtained by a tanning process applied to a substitute of an animal skin or hide. Said leather or leather substitute can be used in the fashion, accessories, household's appliances and other furniture industries, and especially for manufacturing bags, shoes, watch straps, belts or wallets.
Another object of the present invention is a process for cross-linking collagen in a material comprising a step of contacting said material with a compound of formula (I) as defined herein. Said material may in particular be a hide or skin.
Another object of the present invention is a compound of formula (I) per se, as defined herein, with the proviso that said compound is not one of the following compounds (including any stereoisomer thereof):
The invention will also be described in further detail in the following examples, which are not intended to limit the scope of this invention, as defined by the attached claims.

EXAMPLES

Example 1: Preparation of compounds of formula (I)

a) Compounds 3a and 3b

Genipin 1 (5 g, 22.1 mmol) was suspended in dichloromethane (90 mL) under an argon atmosphere. Pyridine (5.5 mL, 68.0 mmol, 3 eq) followed by acetic anhydride (12.5 mL, 132.2 mmol, 6 eq) were added to the mixture while stirring at room temperature. The reaction was followed by TLC (cyclohexane/AcOEt 7/3).
After 2.5 h, MeOH (5 mL, 5.6 eq) was added and the mixture was stirred for 20 minutes. The crude was concentrated under reduced pressure and then filtered on a pad of celite/K₂CO₃. After evaporation of solvents under reduced pressure, the remaining oil was purified by silica gel chromatography (cyclohexane/AcOEt 7:3) to give genipin diacetate 2 (6.74 g, 21.73 mmol, 98%) as a yellow oil.
¹H NMR (300 MHz, CDCl₃) δ (ppm) 7.45 (s, 1H, H-3), 5.93 (br s , 1H, H-7), 5.88 (d, J = 7.3 Hz, 1H, H-1), 4.71 (d, J = 13.5 Hz, 1H, H-10_a), 4.59 (d, J = 13.5 Hz, 1H, H-10_b), 3.74 (s, 3H, OMe), 3.28 (q, J = 7.8 Hz, 1H, H-5), 2.95-2.82 (m, 1H, H-6_a), 2.89-2.82 (m, 1H, H-9), 2.24-2.21 (m, 1H, H-6_b), 2.16 (s, 3H, CH₃ -C=O), 2.08 (3H, s, CH₃ -C=O).
¹³C NMR (75 MHz, CDCl₃) δ (ppm) 170.6 (C=O), 169.4 (C=O), 167.3 (C=O), 151.7 (C-3), 136.6 (C-4), 132.9 (C-7), 111.3 (C-8), 91.8 (C-1), 61.7 (C-10), 51.4 (O=C-O-CH₃), 45.2 (C-9), 38.7 (C-6), 34.7 (C-5), 21.0 (CH₃-C=O), 20.9 (CH₃-C=O).
FT-IR (neat) v (cm^-1) 2951; 2854; 1739; 1705; 1634; 1437; 1378; 1365; 1282; 1221; 1178; 1078.
HRMS (ESI) m/z: calculated for C₁₅H₂₂NO₇ [M + NH₄]⁺ 328.1396 ; found 328,1392.
R_f = 0.44 (SiO₂, cyclohexane/AcOEt 7/3).
Potassium carbonate (2.67 g, 19.34 mmol, 3 eq), potassium ferricyanide (III) (10.61 g, 32.23 mmol, 5 eq), potassium osmate (VI) dihydrate (0.095 g, 0.26 mmol, 0.04 eq), and quinuclidine (0.057 g, 0.51 mmol, 0.08 eq) were suspended in THF/ H₂O (4/5, 57 mL). After 5 min of stirring, methanesulfonamide (0.613 g, 6.45 mmol, 1 eq) was added. Then a solution of genipin diacetate 2 (2.00 g, 6.45 mmol) in THF (7 mL) was added to the reaction mixture. The dark suspension was vigorously stirred at room temperature for 1h and sodium sulfite (4.06 g, 32.21 mmol, 5 eq) was introduced. After 20 min, ethyl acetate (50 mL) was added and the mixture was vigorously stirred overnight. After filtration over a pad of celite, the aqueous layer was extracted with EtOAc. Combined organic layers were washed with HCl aqueous solution (1M), saturated aqueous NaHCO₃ and brine, dried over MgSO₄, filtered, and evaporated under reduced pressure. The obtained yellow oil was purified by silica gel chromatography (dichloromethane/ethyl acetate 1/1) to afford a mixture of both regioisomers 3a and 3b (85:15) as a yellow oil (1.76 g, 5.11 mmol, 79 %, ¹H NMR purity > 95%).
The proportion of 3a vs 3b depends on the reaction time. The longer the reaction was, the more 3b was formed.
3a :
¹H NMR (300 MHz, CDCl₃) δ (ppm) 7.34 (d, J = 1.0 Hz, 1H, H-3), 6.31 (d, J = 3.5 Hz, 1H, H-1), 4,24 (d, J = 12.1 Hz, 1H, H-10a), 4.09 (d, J = 12.1 Hz, 1H, H-10b), 3.95 (br.s/t, 1H, H-7), 3.74 (s, 3H, O-CH₃ ), 3.22 (m, 1H, H-5), 2.67 (dd, J = 9.73 Hz, J = 3.51 Hz, 1H, H-9), 2.30 (m, 1H, H-6a), 2.09 (s, 3H, CH₃ -C=O), 2.08 (s, 3H, CH₃ -C=O), 1.87 (m, 1H, H-6b).
¹³C NMR (75 MHz, CDCl₃) δ(ppm) 171.6 ppm (C=O), 169.4 ppm (C=O), 166.9 (C=O), 150.5 (C-3), 112.2 (C-4), 88.8 (C-1), 79.9 (C-8), 73.3 (C-7), 65.9 (C-10), 51.6 (O=C-O-CH₃), 47.2 (C-9), 36.8 (C-6), 27.3 (C-5), 21.0 (O=C-CH₃), 20.9 (O=C-CH₃).
FT-IR (neat) v (cm^-1) 3464; 2954; 1740; 1706; 1642; 1438; 1372; 1225; 1179; 1081; 1036; 1014; 947; 883; 767.
HRMS (ESI) m/z: calculated for C₁₅H₂₀O₉Na [M + Na]⁺ 367.1005 ; found 367.1002.
R_f = 0.23 (SiO₂, cyclohexane/AcOEt 1/1).
3b :
Due to epimerization on position 1, two diastereoisomers of 3b were obtained.
¹H NMR (300 MHz, CDCl₃) δ (ppm) 7.41 (d, J = 1.1 Hz, 1H, H-3'), 7.39 (d, J = 1.3 Hz, 1H, H-3), 5.53 (t, 1H H-1), 5.27 (m, 1H, H-1'), 5.27 (m, 1H, H-7), 5.11 (q, 1H, H-7') 4,39 (d, J = 11.9 Hz, 1H, H-10a), 4.26 (m, 1H, H-10b, H-10a', H-10b'), 3.72 (s, 3H, O-CH₃ ), 3.71 (s, 3H, O-CH₃ '), 3.35 (m, 1H, H-5), 2.53 (m, 1H, H-9), 2.36 (m, 1H, H-6a'), 2.22 (dd, J = 9.8 Hz, J = 7.1 Hz, 2H, H-6a, H-6b), 2.11 (s, 3H, CH₃ -C=O), 2.10 (s, 3H, CH₃ -C=O, CH₃ -C=O', CH₃ -C=O'), 1.96 (m, 1H, H-6b').
¹³C NMR (75 MHz, CDCl₃) δ(ppm) 171.6 ppm (C=O), 169.4 ppm (C=O), 166.9 (C=O), 150.5 (C-3), 112.2 (C-4), 88.8 (C-1), 79.9 (C-8), 73.3 (C-7), 65.9 (C-10), 51.6 (O=C-O-CH₃), 47.2 (C-9), 36.8 (C-6), 27.3 (C-5), 21.0 (O=C-CH₃), 20.9 (O=C-CH₃).
IR: 3398; 2954; 1706; 1636; 1439; 1373; 1232; 1156; 1081; 1045; 769; 731.
HRMS (ESI) m/z: calculated for C₁₅H₂₀O₉Na [M + Na]⁺ 367.1005 ; found 367.1005.
R_f = 0.31 (SiO₂, cyclohexane/AcOEt 1/1).

b) Compound 4

A mixture of diols 3a and 3b (85/15, 228 mg, 0.66 mmol) was dissolved in dichloromethane (7 mL) under an argon atmosphere. Pyridine (0.16 mL, 1.99 mmol, 3 eq) followed by acetic anhydride (0.37 mL, 3.96 mmol, 6 eq) were added to the mixture while stirring at room temperature. The reaction was followed by TLC (cyclohexane/AcOEt 2/3).
After 19 h, MeOH (0.2 mL) was added and the mixture was stirred for 20 minutes. The crude was concentrated under reduced pressure and then filtered on a pad of celite/K₂CO₃. After evaporation of solvents under reduced pressure, the remaining oil was purified by silica gel chromatography (cyclohexane/AcOEt 85/15 to 70/30) desired product 4 (0.094 g, 0.24 mmol, 37 %, ¹H NMR purity > 95%) as a white solid.
¹H NMR (300 MHz, CDCl₃) δ (ppm) 7.36 (d, J = 0.9 Hz, 1H, H-3), 6.34 (d, J = 2.8 Hz, 1H, H-1), 5.08 (dd, J = 6.1 Hz, J= 3.2 Hz, 1H, H-7), 4,18 (d, J = 12.1 Hz, 1H, H-10a), 4.12 (d, J = 12.1 Hz, 1H, H-10b), 3.72 (s, 3H, O-CH₃ ), 3.26 (m, 1H, H-5), 2.69 (dd, J = 10.3 Hz, J = 2.8 Hz, 1H, H-9), 2.42 (m, 1H, H-6a), 2.10 (s, 3H, CH₃ -C=O), 2.10 (s, 3H, CH₃ -C=O), 2.08 (s, 3H, CH₃ -C=O), 1.94 (m, 1H, H-6b).
¹³C NMR (75 MHz, CDCl₃) δ(ppm) 170.9 ppm (C=O), 170.7 ppm (C=O), 169.0 ppm (C=O), 166.6 (C=O), 150.4 (C-3), 112.3 (C-4), 88.4 (C-1), 80.4 (C-7), 75.8 (C-8), 65.4 (C-10), 51.6 (O=C-O-CH₃), 46.7 (C-9), 35.3 (C-6), 26.7 (C-5), 21.2 (O=C-CH₃), 21.0 (O=C-CH₃), 20.8 (O=C-CH₃).
R_f = 0.23 (SiO₂, cyclohexane/AcOEt 1/1).

c) Compound 6

To a solution of genipin diacetate 2 (1 g, 3.22 mmol) in ethyl acetate (30 mL) under an argon atmosphere, Pd/C catalyst (10 %, 450 mg, 0.42 mmol, 0.13 eq) was added while stirring at rt. Then, the reaction was placed under H₂ atmosphere and stirred at rt (room temperature) for 1h. The flask was flushed with Ar and the mixture was filtered on a short pad of celite. Solvent was evaporated under reduced pressure and the remaining oil was purified by silica gel chromatography (cyclohexane/AcOEt from 95/5 to 80/20) to afford a colourless oil (469 mg) containing 90 % of the desired product 5 (1.67 mmol, 52 %).
¹H-NMR (300 MHz, CDCl₃) δ (ppm) 7.43 (d, J = 1.2 Hz, 1H, H-3), 5.92 (d, J = 6.52 Hz, 1H, H-1), 5.52 (m, 1H, H-8), 3.72 (s, 3H, O-CH₃ ), 3.22 (m, 1H, H-5), 2.79 (m, 1H, H-7), 2.67 (t, J = 7.0 Hz, 1H, H-9), 2.14 (m, 2H, H-6_a and H-6_b), 2.14 (s, 3H, CH₃ -C=O), 1.77 (m, 3H, H-10). R_f = 0.5 (SiO₂, cyclohexane/AcOEt 8/2).
Potassium carbonate (0.31 g, 2.25 mmol, 3 eq), potassium ferricyanide(III) (1.234 g, 3.75 mmol, 5 eq), potassium osmate(VI) dihydrate (0.011 g, 0.03 mmol, 0.04 eq), and quinuclidine (0.006 g, 0.05 mmol, 0.07 eq) were suspended in a mixture H₂O/THF (6 mL, 2/1). After 5 minutes of stirring, the methanesulfonamide (0.075 g, 0.75 mmol, 1 eq) was added. The suspension was cooled to 0 °C and a solution of 5 (0.189 g, 0.75 mmol) in THF (2 mL) was added. The orange suspension was vigorously stirred at 0 °C for 4h and sodium sulfite (0.470 g, 4.5 mmol, 6 eq) was introduced. The reaction mixture was allowed to return to room temperature and, after 30 minutes, filtered over a short pad of celite. The aqueous layer was extracted with EtOAc. Combined organic layers were washed with HCl aqueous solution (1M), saturated aqueous NaHCO₃ and brine, dried over MgSO₄ and evaporated under reduced pressure. The yellow oil obtained was purified by silica gel chromatography (cyclohexane/ethyl acetate 4/6) to afford the targeted diol 6 (0.085 g, 0.30 mmol, 40%, ¹H NMR purity > 95%) as a yellow oil.
¹H NMR (300 MHz, CDCl₃) δ (ppm) 7.33 (d, J = 1.0 Hz, 1H, H-3), 6.33 (d, J = 1.5 Hz, 1H, H-1), 3.71 (m, 1H, H-7), 3.71 (s, 3H, O-CH₃ ), 3.17 (m, 1H, H-5), 2.60 (dd, J = 10.6 Hz, J = 1.5 Hz, 1H, H-9), 2.34 (ddd, J = 14.9 Hz, 9.4 Hz, 2.5 Hz, 1H, H-6a), 2.08 (s, 3H, CH₃ -C=O), 1.72 (m, 1H, H-6b), 1.24 (s, 3H, H-10).
¹³C NMR (CDCl₃, 75Hz) δ (ppm) 169.5 ppm (C=O), 167.2 (C=O), 149.9 (C-3), 112.8 (C-4), 89.7 (C-1), 79.2 (C-8), 78.3 (C-7), 51.5 (O=C-O-CH₃), 46.6 (C-9), 37.7 (C-6), 26.1 (C-5), 21.4 (C-10), 21.1 (O=C-CH₃).
HRMS (ESI) m/z: calculated for C₁₃H₁₈O₇Na [M + Na]⁺ 309.0950 ; found 367.0951.
R_f = 0.18 (SiO₂, cyclohexane/ethyl acetate 1/1).

d) Compound 7

To a vigorously stirred suspension of chromatographic grade silica gel (900 mg) in dichloromethane (15.5 mL), was added dropwise a 0.65 M aqueous solution of NaIO₄ (0.9 mL, 0.59 mmol, 1.4 eq). A flaky suspension was formed. A solution of diol 3a (142 mg, 0.41 mmol) in dichloromethane (20 mL) was then added and the reaction was monitored by TLC (cyclohexane/ethyl acetate 1/1).
After 2h, the reaction suspension was filtered on a sintered glass packed with Na₂SO₄. Solvent was evaporated under reduced pressure to afford the desired pure product 7 (115 mg, 0.34 mmol, 82 %, ¹H NMR purity > 95%) as a yellow oil.
¹H NMR (300 MHz, CDCl₃) δ(ppm) 9.55 (s, 1H, H-7), 7.46 (s, 1H, H-3), 6.25 (d, J = 9.6 Hz, 1H, H-1), 4,81 (d, J = 1.6 Hz, 2H, H-10), 3.71 (m, 1H, H-5), 3.69 (s, 3H, O-CH₃ ), 3.15 (dd, J = 9.6 Hz, J = 5.4 Hz, 1H, H-9), 2.85 (dd, J = 19.1 Hz, J = 9.0 Hz, 1H, H-6a), 2.65 (dd, J = 19.1 Hz, J = 2.8 Hz, 1H, H-6b), 2.13 (s, 3H, O=C-CH₃ ), 2.08 (s, 3H, O=C-CH₃ ).
¹³C NMR (75 MHz, CDCl₃) δ (ppm) 202.1 (C-8), 199.6 (C-7), 170.1 (O=C-CH₃), 168.8 (O=C-CH₃), 166.2 (O=C-O-CH₃), 152.7 (C-3), 108.8 (C-4), 89.3 (C-1), 68.8 (C-10), 51.8 (O=C-O-CH₃), 46.3 (C-9), 45.2 (C-6), 26.8 (C-5), 20.6 (O=C-CH₃), 20.5 (O=C-CH₃).
HRMS (ESI) m/z: calculated for C₁₅H₁₈O₉Na [M + Na]⁺ 365.0849 ; found 365.0849.
FT-IR (neat) v (cm^-1) 2956; 1705; 1639; 1438; 1374; 1228; 1179; 1082; 1047; 940; 794; 768; 731.

e) Compound 8

To a vigorously stirred suspension of chromatographic grade silica gel (596 mg) in dichloromethane (10.5 mL), was added dropwise a 0.65 M aqueous solution of NaIO₄ (0.6 mL, 0.39 mmol, 1.4 eq). A flaky suspension was formed. A solution of diol 6 (81 mg, 0.28 mmol) in dichloromethane (13.5 mL) was then added and the reaction was monitored by TLC (cyclohexane/ethyl acetate 6/4).
After 30 min, the reaction suspension was filtered on a sintered glass packed with Na₂SO₄. Solvent was evaporated under reduced pressure to afford the desired pure product 8 (68 mg, 0.28 mmol, 85%, ¹H NMR purity > 95%) as a yellow oil.
¹H NMR (300 MHz, CDCl₃) δ(ppm) 9.58 ppm (s, 1H, H-7), 7.46 (s, 1H, H-3), 6.25 (d, J = 9.8 Hz, 1H, H-1), 3.80 (m, 1H, H-5), 3.72 (s, 3H, O-CH₃ ), 3.10 (dd, J = 9.8 Hz, J = 5.3 Hz, 1H, H-9), 2.80 (dd, J = 18.8 Hz, J = 8.8 Hz, 1H, H-6a), 2.60 (dd, J = 18.8 Hz, J = 2.8 Hz, 1H, H-6b), 2.29 (s, 3H, H-10) 2.08 (s, 3H, O=C-CH₃).
¹³C NMR (75 MHz, CDCl₃) δ (ppm) 207.0 (C-8), 199.1 (C-7), 168.8 (O=C-CH₃), 164.4 (C-O-CH₃), 152.8 (C-3), 109.2 (C-4), 90.0 (C-1), 51.8 (C-O-CH₃), 50.3 (C-9), 45.5 (C-6), 26.4 (C-5), 20.8 (O=C-CH₃).
R_f = 0.37 (SiO₂, cyclohexane/ethyl acetate 1/1).
FT-IR (neat) v (cm^-1) 3406; 2955; 1706; 1637; 1439; 1374; 1245; 1179; 1082; 939; 768; 731.

Example 2: Tanning experiments using compounds of formula (I)

Collagen powder (200 mg) was immersed in ultrapure water (3 mL, 1500% w/w) in a vial for rehydration. After 24 hours, the rehydrated collagen was filtered and rinsed with ultrapure water.
The tanning compound (10 mg, 5% w/w) was weighed into a brown vial and dissolved in a carbonate buffer solution of pH 10 (1M, 3 mL, 1500% w/w). The rehydrated collagen powder was then added. The sealed vial was heated at 37°C for 48 h with moderate stirring. The collagen powder was finally filtered and thoroughly rinsed with ultrapure water (ca. 20 mL).

Shrinkage temperatures were measured by Differential Scanning Calorimetry (DSC). The temperatures shown in Table 1 are average values.

Table 1

Tanning compound	Shrinkage Temperature	Colour of the collagen powder
Collagen Powder	60 °C	Cream-white
Genipin	83 °C	Dark blue
Compound 2 (comparative)	83 °C	Dark blue
Compound 5 (comparative)	79 °C	Dark green
Compounds 3a + 3b (85/15)	74 °C	Yellow-Orange
Compound 4	75 °C	Yellow-Orange
Compound 6	74 °C	Yellow-Orange
Compound 7	74 °C	Yellow-Orange
Compound 8	74 °C	Yellow-Orange

Tanning experiments on collagen powder (Table 1, Figure 1) show that the compounds of the invention allow to reach shrinkage temperatures which are close to that obtained with genipin. In addition, a light color is obtained with the compounds of the invention, while genipin and derivatives 2 and 5 impart a dark color to the hide.

Impact of the tanning conditions on a tanning process using compounds 6a and 6b

The previous protocol is repeated with compounds 6a and 6b. A parameter chosen among the tanning time (Table 2), the temperature (Table 3), the tanning agent content (Table 4) or the buffer solution (Table 5) is modified. The influence of the said parameter is assessed by comparing the shrinkage temperatures.

Experiments described in Tables 2 to 5 show that the compounds of the invention are versatile tanning agents, which can be used in various conditions. Moreover, Table 4 shows that a limited amount, e.g 5%, of the tanning agent is needed to give optimum tanning. When compared to WO2009/065915 and Schröpfer and Meyer (IULTCS Congress Dresden, 2019), which describe the use of iridoids extracts, the compounds of the invention can be used in a much lower amount, which allows a lower organic content of the effluent.

Table 2

Tanning agent	Tanning time	Shrinkage temperature	Colour of the collagen powder
Compounds 3a + 3b	48 h	74 °C	Yellow-Orange
Compounds 3a + 3b	24 h	74 °C	Yellow-Orange

Table 3

Tanning agent	Tanning temperature	Shrinkage temperature	Colour of the collagen powder
Compounds 3a + 3b	37 °C	74 °C	Yellow-Orange
Compounds 3a + 3b	20 °C	72 °C	Light yellow

Table 4

Tanning agent	Tanning agent content (w/w)	Shrinkage temperature	Colour of the collagen powder
Compounds 3a + 3b	1%	65 °C	Pale yellow
Compounds 3a + 3b	3%	72 °C	Light yellow
Compounds 3a + 3b	5%	74 °C	Yellow-Orange
Compounds 3a + 3b	10%	72 °C	Yellow-Orange
Compounds 3a + 3b	20%	71 °C	Yellow-Brown

Table 5

Tanning agent	Buffer solution	Shrinkage temperature	Colour of the collagen powder
Compounds 3a + 3b	pH 10 (Carbonate 1 M)	74 °C	Yellow-Orange
Compounds 3a + 3b	pH 10 (Carbonate 0.5 M)	73 °C	Yellow
Compounds 3a + 3b	pH 9 (Phosphate 0.5 M)	75 °C	Orange-Brown
Compounds 3a + 3b	pH 8 (Phosphate 0.5 M)	74 °C	Pale yellow
Compounds 3a + 3b	pH 7 (Phosphate 0.5 M)	72 °C	Pale yellow

Example 3: Tanning of calf hide with compounds 3a and 3b

The tanning 3a + 3b compound (600 mg, 5% w/w) was dissolved in a citric acid - sodium hydrogenophosphate buffer solution of pH 7.4 (40 mL, 300% w/w). The delimed calf hide (5 cm x 5 cm, 12 g) was then added. The tanning solution was agitated and heated at 35 °C in a shaking water bath. After 48 h, the tanned hide was thoroughly rinsed with water and added in a solution of gallnut (retanning agent, 1.6 g, 13% w/w) in water at pH 7 (40 mL, 300% w/w). After 2h of shaking, BM 80 (fatliquor, 400 mg, 3% w/w) was added and the solution heated at 50 °C overnight. Finally, pH was downed to 3.5 with acetic acid and the solution shaked for 24h more. The sample was dried at room temperature giving a slightly beige color leather (Figure 2).
Shrinkage temperature T_S was measured according to EN ISO 3380.
T_S = 76 °C

Claims

Use of a compound represented by the following formula (I), in a tanning process: wherein:
- R₁ is a hydrogen atom, a C₁-C₁₂ aliphatic group, aryl, -C(O)-(C₁-C₁₂ aliphatic group), -C(O)-(aryl), -CH₂-O-(C₁-C₁₂ aliphatic group), or -CH₂-O-(aryl), said aliphatic groups being each independently optionally substituted by an aryl, a halide, -OH, -O-(C₁-C₁₂ aliphatic group), - N(C₁-C₁₂ aliphatic group)(C₁-C₁₂ aliphatic group), -O-C(O)-(C₁-C₁₂ aliphatic group), -C(O)-O-(C₁-C₁₂ aliphatic group), -C(O)-NH-(C₁-C₁₂ aliphatic group), -NH-C(O)-(C₁-C₁₂ aliphatic group), -NH-C(O)-NH-(C₁-C₁₂ aliphatic group), -NH-C(O)-O-(C₁-C₁₂ aliphatic group), -O-C(O)-NH-(C₁-C₁₂ aliphatic group), or -O-C(O)-O-(C₁-C₁₂ aliphatic group),

- R₂ is a hydrogen atom or a (C₁-C₁₂) aliphatic group,

- R₃ is -CH₂-C(O)H or -CH₂-CH₂-OH,

- R₄ is -C(O)-CH₂-R₅ or -CH(OH)-CH₂-R₅', where R₅ and R₅' are each independently a hydrogen atom, a C₁-C₁₂ aliphatic group, -OH, or -O-C(O)-(C₁-C₁₂ aliphatic group),
or R₃ and R₄ form together the following chain of formula (II): wherein R₆, R₇, R₈, and R₉ are each independently a hydrogen atom, -OH, or -O-C(O)-(C₁-C₁₂ aliphatic group),
or a salt thereof.
Use according to claim 1, wherein R₁ is a hydrogen atom or -C(O)-(C₁-C₁₂ aliphatic group), preferably a hydrogen atom or -C(O)-(C₁-C₆ alkyl).
Use according to claim 1 or 2, wherein R₂ is a C₁-C₁₂ aliphatic group, preferably a C₁-C₆ alkyl.
Use according to any one of claims 1 to 3, wherein R₄ is -C(O)-CH₂-R₅, where R₅ is a hydrogen atom or -O-C(O)-(C₁-C₁₂ aliphatic group), preferably a hydrogen atom or -O-C(O)-(C₁-C₆ alkyl).
Use according to any one of claims 1 to 4, wherein R₆ is hydrogen.
Use according to any one of claims 1 to 5, wherein R₇ is -OH or -O-C(O)-(C₁-C₁₂ aliphatic group), preferably -OH or -O-C(O)-(C₁-C₆ alkyl).
Use according to any one of claims 1 to 6, wherein R₈ is -OH.
Use according to any one of claims 1 to 7, wherein R₉ is a hydrogen atom or -O-C(O)-(C₁-C₆ alkyl).
Use according to claim 1, wherein said compound is one of the following compounds:
Use according to claim 1, wherein said compound is one of the following compounds:
Use according to any one of claims 1 to 10, for tanning a hide or a skin.
Use according to any one of claims 1 to 10, for tanning a collagen-containing material.
A method for manufacturing a leather or a leather substitute comprising the use according to any one of claims 1 to 10.
A compound which is represented by the following formula (I): wherein:
- R₁ is a hydrogen atom, a C₁-C₁₂ aliphatic group, aryl, -C(O)-(C₁-C₁₂ aliphatic group), -C(O)-(aryl), -CH₂-O-(C₁-C₁₂ aliphatic group), -CH₂-O-(aryl), said aliphatic groups being each independently optionally substituted by an aryl, a halide, -OH, -O-(C₁-C₁₂ aliphatic group), - N(C₁-C₁₂ aliphatic group)(C₁-C₁₂ aliphatic group), -O-C(O)-(C₁-C₁₂ aliphatic group), -C(O)-O-(C₁-C₁₂ aliphatic group), -C(O)-NH-(C₁-C₁₂ aliphatic group), -NH-C(O)-(C₁-C₁₂ aliphatic group), -NH-C(O)-NH-(C₁-C₁₂ aliphatic group), -NH-C(O)-O-(C₁-C₁₂ aliphatic group), -O-C(O)-NH-(C₁-C₁₂ aliphatic group), or -O-C(O)-O-(C₁-C₁₂ aliphatic group),

- R₂ is a hydrogen atom or a (C₁-C₁₂) aliphatic group,

- R₃ is -CH₂-C(O)H or -CH₂-CH₂-OH,

- R₄ is -C(O)-CH₂-R₅ or -CH(OH)-CH₂-R₅', where R₅ and R₅' are each independently a hydrogen atom, a C₁-C₁₂ aliphatic group, -OH, or -O-C(O)-(C₁-C₁₂ aliphatic group),
or R₃ and R₄ form together the following chain of formula (II): wherein R₆, R₇, R₈, and R₉ are each independently a hydrogen atom, -OH, or -O-C(O)-(C₁-C₁₂ aliphatic group),
or a salt thereof,

with the proviso that said compound is not one of the following compounds:
The compound according to claim 14, which is defined as in any one of claims 2 to 9.
A process for cross-linking collagen in a material comprising a step of contacting said material with a compound as defined in any one of claims 1 to 10.
The process according to claim 16, wherein said material is a hide or skin.