生物质催化转化制备戊二醇和己二醇

高级二元醇是重要的化工中间体，其中1，5-戊二醇和1，6-己二醇是具有高附加值的精细化工产品，广泛应用于增塑剂、高级油墨、化妆品、医药、光固化（UV）涂料等领域。该文综述了生物质基1，5-戊二醇和1，6-己二醇制备技术的研究现状，与石油基路径相比，生物质基路径具有原料可再生、资源丰富、转化路线短（2-~3步转化）、产物选择性高（大于90%）及水相反应体系绿色无污染等优点，但还存在铂、铑、铼、铱等贵金属催化剂昂贵、转化率偏低和碳氧键断裂机理研究不足等问题。进一步开发非贵金属替代贵金属催化剂和提高贵金属利用率、新的高效制备路径和明晰碳氧键选择性断裂机理具有非常重要的意义。     

Screening,Molecular Cloning,and Biochemical Characterization of an Alcohol Dehydrogenase from Pichia pastoris Useful for the Kinetic Resolution of a Racemic β‐Hydroxy‐β‐trifluoromethyl Ketone

The stereoselective synthesis of chiral 1,3‐diols with the aid of biocatalysts is an attractive tool in organic chemistry. Besides the reduction of diketones, an alternative approach consists of the stereoselective reduction of β‐hydroxy ketones (aldols). Thus, we screened for an alcohol dehydrogenase (ADH) that would selectively reduce a β‐hydroxy‐β‐trifluoromethyl ketone. One potential starting material for this process is readily available by aldol addition of acetone to 2,2,2‐trifluoroacetophenone. Over 200 strains were screened, and only a few yeast strains showed stereoselective reduction activities. The enzyme responsible for the reduction of the β‐hydroxy‐β‐trifluoromethyl ketone was identified after purification and subsequent MALDI‐TOF mass spectrometric analysis. As a result, a new NADP⁺‐dependent ADH from Pichia pastoris (PPADH) was identified and confirmed to be capable of stereospecific and diastereoselective reduction of the β‐hydroxy‐β‐trifluoromethyl ketone to its corresponding 1,3‐diol. The gene encoding PPADH was cloned and heterologously expressed in Escherichia coli BL21(DE3). To determine the influence of an N‐ or C‐terminal His‐tag fusion, three different recombinant plasmids were constructed. Interestingly, the variant with the N‐terminal His‐tag showed the highest activity; consequently, this variant was purified and characterized. Kinetic parameters and the dependency of activity on pH and temperature were determined. PPADH shows a substrate preference for the reduction of linear and branched aliphatic aldehydes. Surprisingly, the enzyme shows no comparable activity towards ketones other than the β‐hydroxy‐β‐trifluoromethyl ketone.     

不对称邻二醇的合成及其在有机合成中的应用

综述了对称邻二醇的合成和选择性转换，以及它在立体控制催化剂和天然产物不对称合成等方面的应用。     

Mg/Al水滑石催化合成聚碳酸酯二醇的研究

制备了Mg-Al水滑石,并将其进行了焙烧和再水合的处理,运用XRD,IR和BET对3种催化剂进行了表征,并对其应用于催化合成聚碳酸酯二醇(PCDL)的反应进行了研究.     

A novel route to α,ω-telechelic poly(-caprolactone) diols, precursors of biodegradable polyurethanes, using catalysis by decamolybdate anion

A new convenient route for the synthesis of poly(-caprolactone) (PCL) with α,ω-telechelic diols' end-groups is presented. Synthesis of α,ω-telechelic PCL diols (HOPCLOH) was achieved by ring-opening polymerization (ROP) of -caprolactone (CL) catalyzed with ammonium decamolybdate (NH₄)₈[Mo₁₀O₃₄] and using diethylene glycol (DEG) as initiator. Obtained HOPCLOH was characterized by ¹H and ¹³C NMR, FT-IR, GPC and MALDI-TOF. Comparative studies demonstrate that ammonium decamolybdate (NH₄)₈[Mo₁₀O₃₄] is better catalyst than Sn-octanoate (SnOct₂) toward CL polymerization in presence of DEG, under the conditions tested. A biodegradable poly(ester-urethane-urea) derivative was efficiently prepared from synthesized HOPCLOH. Obtained polymer shows minor differences with respect to the properties recorded for a poly(ester-urethane-urea) obtained from commercial HOPCLOH.     

Exploring the Biocatalytic Scope of Alditol Oxidase from Streptomyces coelicolor

The substrate scope of the flavoprotein alditol oxidase (AldO) from Streptomyces coelicolor A3(2), recombinantly produced in Escherichia coli, was explored. While it has been established that AldO efficiently oxidizes alditols to D ‐aldoses, this study revealed that the enzyme is also active with a broad range of aliphatic and aromatic alcohols. Alcohols containing hydroxy groups at the C‐1 and C‐2 positions like 1,2,4‐butanetriol (K_m=170 mM, k_cat=4.4 s⁻¹), 1,2‐pentanediol (K_m=52 mM, k_cat=0.85 s⁻¹) and 1,2‐hexanediol (K_m=97 mM, k_cat=2.0 s⁻¹) were readily accepted by AldO. Furthermore, the enzyme was highly enantioselective for the oxidation of 1,2‐diols [e.g., for 1‐phenyl‐1,2‐ethanediol the (R)‐enantiomer was preferred with an E‐value of 74]. For several diols the oxidation products were determined by GC‐MS and NMR. Interestingly, for all tested 1,2‐diols the products were found to be the α‐hydroxy acids instead of the expected α‐hydroxy aldehydes. Incubation of (R)‐1‐phenyl‐1,2‐ethanediol with ¹⁸O‐labelled water (H₂¹⁸O) revealed that a second enzymatic oxidation step occurs via the hydrate product intermediate. The relaxed substrate specificity, excellent enantioselectivity, and independence of coenzymes make AldO an attractive enzyme for the preparation of optically pure 1,2‐diols and α‐hydroxy acids.     

An Alcohol Dehydrogenase from the Short-Chain Dehydrogenase/Reductase Family of Enzymes for the Lactonization of Hexane-1,6-diol

Biocatalytic production of lactones, and in particular ϵ-caprolactone (CL), have gained increasing interest as a greener route to polymer building blocks, especially through the use of Baeyer–Villiger monooxygenases (BVMOs). Despite several advances in the field, BVMOs, however, still suffer several practical limitations. Alcohol dehydrogenase (ADH)-mediated lactonization of diols in turn has received far less attention and very few enzymes have been identified for the conversion of diols to lactones, with horse-liver ADH (HLADH) remaining the catalyst of choice. Screening of a diverse panel of ADHs, AaSDR-1, a member of the short-chain dehydrogenase/reductase family, was found to produce ϵ-caprolactone from hexane-1,6-diol. Moreover, cofactor regeneration by an NADH oxidase eliminated the requirement of co-substrates, yielding water as the sole by-product. Despite lower turnover frequencies as compared to HLADH, higher selectivity was found for the production of CL, with HLADH forming significant amounts of 6-hydroxyhexanoic acid and adipic acid through aldehyde dehydrogenation/oxidation of the gem-diol intermediates. Also, CL yield were shown to be dependent on buffer choice, as structural elucidation of a Tris adduct confirmed the buffer amine to react with aliphatic aldehydes forming a Schiff-base intermediate which through further ADH oxidation, forms a tricyclic acetal product.     

Characterization of four diol dehydrogenases for enantioselective synthesis of chiral vicinal diols

Enantiopure vicinal diols are important building blocks used in the synthesis of fine chemicals and pharmaceutical compounds. Diol dehydrogenase (DDH) mediated stereoselective oxidation of racemic vicinal is an efficient way to prepare enantiopure vicinal diols. In this study, four new bacterial DDHs (AnDDH from Anoxybacillus sp. P3H1B, HcDDH from Hazenella coriacea, GzDDH from Geobacillus zalihae and LwDDH from Leptotrichia wadei) were mined from the GenBank database and expressed in E. coli T7. The four DDHs were purified and biochemically characterized for oxidation activity toward (R)-1-phenyl-1,2-ethanediol, with the optimal reaction condition of pH9.0 (AnDDH), 10.0 (HcDDH) and 11.0 (GzDDH and LwDDH) and the temperatures at 40℃ (AnDDH), 50℃ (HcDDH) and 60℃ (GzDDH and LwDDH), respectively. The four enzymes were stable at the pH from 7.0 to 9.0 and below 40℃. Kinetic parameters of four DDHs showed that the HcDDH from Hazenella coriacea had high activity toward a broad range of vicinal diols. A series of racemic vicinal diols were successfully resolved by recombinant E. coli (HcDDH-NOX) resting cells co-expression of an NADH oxidase (NOX), affording (S)-diols and (1S, 2S)-trans-diols in ≥ 99% ee. The synthetic potential of HcDDH was proved by E. coli (HcDDH-NOX) via kinetic resolution of racemic trans-1,2-indandiol on a 100 ml scale reaction, (S, S)-trans-1,2-indandiol was prepared in 46.7% yield and >99% ee. In addition, asymmetric reduction of four α-hydroxy ketones (10-300 mmol·L^-1) by E. coli (HcDDH-GDH) resting cells resulted in >99% ee and 69-98% yields of (R)-vicinal diols. The current research expands the toolbox of DDHs to synthesize chiral vicinal diols and demonstrated that the mined HcDDH is a potential enzyme in the synthesis of a broad range of chiral vicinal diols.     

Poly(ε-caprolactone) Diols (HOPCLOH) and Their Poly(ester-urethanes) (PEUs): The Effect of Linear Aliphatic Diols [HO–(CH2)m–OH] as Initiators

α,ω-Hydroxy telechelic poly(ε-caprolactones) were prepared by ring-opening polymerization of the ε-caprolactone catalyzed by ammonium decamolybdate in the presence of different aliphatic diols [HO–(CH₂)_m–OH, where m?=?2, 4, 6, 8, 10, 12, 14, and 16] as initiators to obtain a family of α,ω-hydroxy telechelic poly(ε-caprolactone) [HO–PCL–O–(CH₂)_m–O–PCL–OH, m?=?2, 4, 6, 8, 10, 12, 14, and 16]. The content of the alkyl group (AG) (–(CH₂)_m–) had an important effect on the crystallinity (x_i) of α,ω-hydroxy telechelic poly(ε-caprolactone), showing a proportional relationship. In poly(ester-urethanes) derived from α,ω-hydroxy telechelic poly(ε-caprolactones) and 1,6-hexamethylene diisocyanate, the AG also showed a similar effect on the x_i and eventually on the mechanical properties, increasing the values of the modulus. Therefore, AG content was a factor to induce a plastic behavior in poly(ester-urethanes). The effect of AG on the water uptake of poly(ester-urethanes) after 1 week was negligible.