Macrobisphenols are a family of bio-inspired bisphenols introduced in 2013, composed of two p-hydroxycinnamate units linked through ester bonds via a polyol scaffold. Unlike bisphenol A, macrobisphenols are non-endocrine-disrupting compounds, and display outstanding antiradical activity, making them attractive, safer alternatives for polymer-related applications. Their versatility enables use as plasticizers, antioxidants, and monomers for polymer and materials synthesis. Over the past 12 years, substantial progress has been made to enhance their industrial viability by expanding structural diversity through extensive libraries of analogs, significantly lowering production costs, and minimizing environmental impact through greener synthetic strategies. This article critically reviews the evolution of macrobisphenol synthesis, highlights recent advances in sustainable and scalable pathways, and provides practical guidelines for selecting the most cost-effective and environmentally responsible processes according to the targeted structure.

Alkylresorcinols are natural phenolipids exhibiting interesting properties (e.g., antioxidant, anticancer). To monitor their bioproduction or quantify them in food samples, standards are required. However, due to their odd long alkyl chain (C > 15), only a few synthetic routes are available, with the most efficient ones relying on the Wittig reaction. To provide a more sustainable synthetic route, two major modifications were implemented: (i) the starting material was changed from 3,5-dimethoxybenzaldehyde to 3,5-dibenzyloxybenzaldehyde, thereby eliminating the need for demethylation with highly toxic reagents such as BBr3 or HBr; and (ii) the solvent system was replaced with greener and safer alternatives - cyclopentyl methyl ether and isopropyl alcohol - instead of the toluene, dimethyl sulfoxide, and dichloromethane used in previous publications. This strategy also enabled the replacement of a four-step sequence with two one-pot two-step reactions, resulting in good overall yields of 66 % and 60 % for C:19 and C:21 alkylresorcinols, respectively.

This study focuses on the synthesis of fully renewable polycarbonates (PCs) starting from cellulose-based platform molecules levoglucosenone (LGO) and 2,5-bis(hydroxymethyl)furan (BHMF). These unique bio-based PCs are obtained through the reaction of a citronellol-containing triol (Triol-citro) derived from LGO, with a dimethyl carbonate derivative of BHMF (BHMF-DC). Solvent-free polymerizations are targeted to minimize waste generation and promote an eco-friendly approach with a favorable environmental factor (E-factor). The choice of metal catalyst during polymerization significantly influences the polymer properties, resulting in high molecular weight (up to 755 kDa) when Na2CO3 is employed as an inexpensive catalyst. Characterization using nuclear magnetic resonance confirms the successful incorporation of the furan ring and the retention of the terminal double bond of the citronellol pendant chain. Furthermore, under UV irradiation, the presence of both citronellol and furanic moieties induces singular structural changes, triggering the formation of three distinct structures within the polymer network, a phenomenon herein occurs for the first time in this type of polymer. These findings pave the way to new functional materials prepared from renewable monomers with tunable properties. This study explores the synthesis of renewable polycarbonates using both levoglucosenone and 5-hydroxymethyl furfural as renewable platform molecules. A solvent-free polymerization approach with a low E-factor is detailed. The influence of metal catalysts on polymer properties is examined, with Na2CO3 yielding a high molecular weight of 755 kDa. UV irradiation induces unique structural changes within the polymer network.image

It is not unusual for naturally occurring compounds to be limited for their use in cosmetics due to their low water solubility. Recently, aiming at accessing novel phlorizin (a glycosylated bioactive recovered from apple tree wood and already used in cosmetics as antioxidant ingredient) analogues, we reported the synthesis of very promising - but low water-soluble - biomass-derived chalcones (CHs) and dihydrochalcones (DHCs) exhibiting antioxidant and anti-tyrosinase activities. Glycosylating bioactive compounds being one of the most common strategies to increase their water solubility, herein we report the enzymatic glycosylation of the CHs mentioned above, as well as DHC using cyclodextrin glycosyltransferases (CGTase), enzymes well-known for catalyzing the selective α(1→4) transglycosylation. Indeed, while most natural glycosides are β-glycosides (such as phlorizin), the selected enzyme produces selectively new α-glycosides, thus expanding their structural diversity. A first step of separation using Centrifugal Partition Chromatography (CPC) led to mono-, di- or triglycosides-enriched fractions, which were then submitted to a comprehensive purification strategy for an in-depth chemical profiling of the synthesized α-glycosides, revealing that the major compounds were glycosylpyranosides. Surprisingly, among the diglycosides characterized, besides the expected maltoside compounds, nigeroside derivatives were also identified in significant amounts, depending on the starting compound structure. Finally, evaluating the antiradical, anti-tyrosinase and antimicrobial activities of the major glycosides revealed them as potential sustainable alternatives to current petro-sourced cosmetic ingredients.

Rhamnolipids (RLs) are highly valuable molecules in the cosmetic, pharmaceutic, and agricultural sectors with outstanding biosurfactant properties. In agriculture, due to their potential to artificially stimulate the natural immune system of crops (also known as elicitation), they could represent a critical substitute to conventional pesticides. However, their current synthesis methods are complex and not aligned with green chemistry principles, posing a challenge for their industrial applications. In addition, their bioproduction is cumbersome with reproducibility issues and expensive downstream processing. This work offers a more straightforward and green access to RLs, crucial to decipher their mechanisms of action and design novel potent and eco-friendly elicitors. To achieve this, we propose an efficient seven-step synthetic pathway toward (R)-3-hydroxyfatty acid chains present in RLs, starting from cellulose-derived levoglucosenone, with Michael addition, Baeyer–Villiger oxidation, Bernet–Vasella reaction, and cross-metathesis homologation as key steps. This method allowed the production of (R)-3-hydroxyfatty acid chains and derivatives with an overall yield ranging from 24% to 36%.

Sinapoyl malate, naturally present in plants, has proved to be an exceptional UV filter and molecular heater for plants. Although there are nowadays industrially relevant sustainable synthetic routes to sinapoyl malate, its incorporation into certain cosmetic formulations, as well as its adsorption on plant leaves, is limited by its hydrophilicity. To overcome these obstacles, it is important to find a way to effectively control the hydrophilic-lipophilic balance of sinapoyl malate to make it readily compatible with the cosmetic formulations and stick on the waxy cuticle of leaves. To this end, herein, we describe a highly regioselective chemo-enzymatic synthesis of sinapoyl malate analogues possessing fatty aliphatic chains of variable length, enabling the lipophilicity of the compounds to be modulated. The potential toxicity (i.e., mutagenicity, carcinogenicity, endocrine disruption, acute and repeated-dose toxicity), bioaccumulation, persistence and biodegradability potential of these new analogues were evaluated in silico, along with the study of their transient absorption spectroscopy, their photostability as well as their photodegradation products.

Recently, a renewable five-membered lactone containing citronellol (HBO-citro) was synthesized from levoglucosenone (LGO). A one-pot two-step pathway was then developed to produce a mixture of 5- and 6-membered Lactol-citro molecules (5ML and 6ML, respectively) from HBO-citro. Proton nuclear magnetic resonance (1H NMR) of a mixture of 5ML and 6ML at varying temperatures showed that the chemical shifts of the hydroxyls, as well as the 5ML:6ML ratio, are temperature-dependent. Indeed, a high temperature, such as 65 °C, led to an up-field shielding of the hydroxyl protons as well as a drop in the 5ML:6ML ratio. The monomers 5ML and 6ML were then engaged in polycondensation reactions involving diacyl chlorides. Renewable copolyesters with low glass transition temperatures (as low as −67 °C) and cross-linked citronellol chains were prepared. The polymers were then hydrolyzed using a commercial lipase from Thermomyces lanuginosus (Lipopan® 50 BG). A higher degradation rate was found for the polymers prepared using Lactol-citro molecules, compared to those obtained by the polycondensation reactions of diacyl chlorides with Triol-citro—a monomer recently obtained by the selective reduction of HBO-citro.

The bio-based platform (S)-γ-hydroxymethyl-γ-butyrolactone, whose sustainable kiloscale-synthesis from cellulose-derived levoglucosenone has been validated, is valorized into new potential bio-based surfactants mechano-synthesized in solventless conditions.

Cellulose-derived photocrosslinkable polycarbonates with renewable citronellol pendant chains were synthesised via polycondensation of Triol-citro, a levoglucosenone-based triol monomer, and dimethoxycarbonyl isosorbide.

The homopolymerization in basic conditions of the recently reported bis(gamma-lactone), 2H-HBO-HBO, is herein described for the first time. The solvent-free polymerization of this pentafunctional levoglucosenone (LGO) derivative affords fully renewable poly(vinyl-ether lactone) copolymers with a highly hyperbranched structure. This investigation stems from the polycondensation trials between 2H-HBO-HBO and di(methyl carbonate) isosorbide (DCI) that fails to give the anticipated polycarbonates. Such unexpected behavior is ascribed to the higher reactivity of the 2H-HBO-HBO hydroxy groups toward its alpha,beta-conjugated endocyclic CC, rather than the DCI methylcarbonate moieties. The different mechanistic scenarios involved in 2H-HBO-HBO homopolymerization are addressed and a possible structure of poly(2H-HBO-HBO) is suggested. Furthermore, the readily accessible (S)-gamma-hydroxymethyl-alpha,beta-butenolide (HBO) is also polymerized for the first time at a relatively large scale, without any prior modification, resulting in a new hyperbranched polymer with an environmental factor (E factor) approximate to 0. These new HBO-based polymers have a great potential for industrial-scale production due to their interesting properties and easy preparation via a low-cost, green, and efficient process.

Levoglucosenone (LGO) is a cellulose-derived molecule that is present commercially on a multi-ton/year scale. Taking advantage of the α,β-conjugated ketone of LGO, a new citronellol-containing 5-membered lactone (HBO-citro) was synthesized through a one-pot two-step pathway involving oxa-Michael addition and Baeyer-Villiger oxidation. The solvent-free treatment of HBO-citro with NaBH4 at room temperature led to the full reduction of the lactone moiety which gave a novel fully renewable triol monomer having a citronellol side chain (Triol-citro). Noticeably, by simply changing the reducing agent, temperature and reaction duration, the partial reduction of HBO-citro can be achieved to yield a mixture of 5- and 6-membered Lactol-citro molecules. Triol-citro was chosen to prepare functional renewable polyesters having citronellol pendant chains via polycondensation reactions with diacyl chlorides having different chain lengths. Good thermal stability (Td5% up to 170 °C) and low glass transition temperatures (as low as −42 °C) were registered for the polyesters obtained. The polymers were then hydrolyzed using a commercial lipase from Thermomyces lanuginosus (Lipopan® 50 BG) to assess their biodegradability. A higher degradation profile was found for the polyesters prepared using co-monomers (acyl chlorides) having longer chain lengths. This is likely due to the decreased steric hindrance around the ester bonds which allowed enhanced accessibility of the enzyme.

Levoglucosenone (LGO) is a cellulose-derived and commercially available platform molecule that is produced at an industrial scale. LGO contains a highly reactive double bond that was used to produce two isomers of norbornene-containing LGO monomers, endo-N-LGO (1) and exo-N-LGO (2). Furthermore, Baeyer-Villiger oxidation of 1 was performed to yield a highly-valuable chiral monomer, endo-N-HBO (3). The norbornene moiety of the prepared monomers was readily polymerized by ring-opening metathesis polymerization (ROMP) in the presence of GI catalyst to access highly thermostable polymers with T-d5% up to 360 degrees C in the case of N-LGO-based polymers and T-d5% in the range of 374-380 degrees C when 3 was polymerized, such range of T-d5% being the highest reported up-to-date for the LGO-derived polymers. The effect of monomer concentration over the polymerization process was studied and showed that 4 M solutions lead to a better monomer conversion while preserving the control over the polymer structure and reducing the environmental factor (E factor). GI was found active in the ROMP of 3 without the need of protecting the hydroxy group and thus leading to pendent hydroxy functional polymers. Furthermore, for the first time, copolymers containing both LGO and HBO reactive moieties were prepared by random copolymerization of 1 and 3.

The levoglucosenone-based norbornenes family was extended to include a new bi-functional methacrylate monomer that, upon ROMP in Cyrene™, leads to polymers with pendent methacrylate moieties which can be modified by post-polymerization reactions.

Naturally occurring sinapine was successfully synthesized through a proline-mediated Knoevenagel-Doebner condensation in ethanol. This synthetic process involving biobased syringaldehyde, Meldrum's acid, and choline chloride offers a sustainable alternative to the existing low-yield pathways. This two-step strategy gives access to sinapine in a 52% overall yield and has been implemented in the synthesis of sinapine analogues, using 4-hydroxybenzaldehyde, 3,4-dihydroxybenzaldehyde, and vanillin as precursors, giving target molecules with 34-61% overall isolated yields. The purity of synthetic sinapine and its analogues (ca. 95%) was assessed by NMR and high-performance liquid chromatography-mass spectrometry analyses. Furthermore, the antioxidant and antimicrobial activities were assessed, and the potential of this series of molecules was confirmed.

Naturally occurring p-hydroxycinnamic acids were obtained in good yields (50-85%) using a pyridine/piperidine-free Knoevenagel Doebner condensation of the corresponding p-hydroxybenzaldehydes with malonic acid in ethanol. This method uses fully renewable and cheap nontoxic reagents and solvents. By combination of a design of experiments (DoE) and a one variable at a time optimization (OVAT), the different reaction parameters were optimized in order to favor p-hydroxycinnamic acids production over that of the two other reaction byproducts, the corresponding diacid and vinylphenol.

This paper reports the preparation, characterization, and performance of three low viscosity fully bio-based benzoxazine resins synthesized from bio-based furfurylamine, paraformaldehyde, and three new enzymatic originated diphenols obtained through a sustainable and highly selective lipase-catalyzed enzymatic process from p-coumaric acid, and three bio-based diols (propanediol, butanediol, and isosorbide, respectively). The enzymatic method is used for the first time, to the authors' knowledge, to design specific diphenolic structures dedicated to the preparation of benzoxazine thermosetting resins whose precursors exhibit easy handling within a wide processing window (from room temperature up to 200 degrees C). The resulting cross-linked materials present high glass transition temperature (T-g > 200 degrees C) and inherent charring ability upon pyrolysis (approximate to 50 wt% at 1000 degrees C). These results open a valuable and new pathway to develop enhanced benzoxazines and bring them new properties.

A diastereoselective chemoenzymatic synthetic pathway to D‐(+)‐ribono‐1,4‐lactone, a versatile chiral sugar derivative widely used for the synthesis of various natural products, has been designed from cellulose‐based levoglucosenone (LGO). This route involves a sustainable Baeyer‐Villiger oxidation of LGO to produce enantiopure (S)‐γ‐hydroxymethyl‐α,β‐butenolide (HBO) that is further functionalized with various protecting groups to provide 5‐O‐protected γ‐hydroxymethyl‐α,β‐butenolides. The latter then undergo a diastereoselective and high‐yielding syn‐dihydroxylation of the α,β‐unsaturated lactone moiety followed by a deprotection step to give D‐(+)‐ribono‐1,4‐lactone. Through this 4‐step synthetic route from LGO, D‐(+)‐ribono‐1,4‐lactone is obtained with d.r. varying from 82:18 to 97:3 and in overall yields between 32 and 41 % depending on the protecting group used. Moreover, valuable synthetic intermediates 5‐O‐tert‐butyldimethylsilyl‐, 5‐O‐tert‐butyldiphenylsilyl‐ as well as 5‐O‐benzyl‐ribono‐1,4‐lactones are obtained in 3 steps from LGO in 58, 61 and 40 %, respectively.