Asymmetric synthesis of thymine nucleoside analogues based on the isochroman core

Diastereoisomeric analogues of d4T having an isochroman core as the glycone moiety have been prepared in seven steps. Starting from phthalaldehyde, two chiral centres analogous to the α/β anomers of D/L sugars were created. The first was obtained enantiomerically pure via asymmetric dihydroxylation and the second via cyclisation of an aldehyde group with a primary hydroxyl group. Retention of chiral integrity at the C₄ site enabled enantiomerically pure nucleoside analogues to be obtained.     

Total synthesis of (±) maculalactone A, maculalactone B and maculalactone C and the determination of the absolute configuration of natural (+) maculalactone A by asymmetric synthesis

Maculalactones A, B and C from the marine cyanobacterium Kyrtuthrix maculans are amongst the only compounds based on the tribenzylbutyrolactone skeleton known in nature and (+) maculalactone A from the natural source possesses significant biological activity against various marine herbivores and marine settlers. We now report a concise synthesis of racemic maculalactone A in five steps from inexpensive starting materials. Maculalactones B and C were synthesized by a minor modification to this procedure, and the synthetic design also permitted an asymmetric synthesis of maculalactone A to be achieved in around 85% ee. The (+) and (−) enantiomers of maculalactone A were assigned, respectively, to the S and R configurations on the basis of the chiral selectivity expected for catecholborane reduction of an unsymmetrical ketone in the presence of Corey's oxazoborolidine catalyst. Surprisingly, it appeared that natural (+) maculalactone A was biosynthesized in K. maculans in a partially racemic form, comprising ca. 90-95% of the (S) enantiomer and 5-10% of its (R) enantiomer. Coincidentally therefore, the percentage enantiomeric excess of the product obtained from asymmetric synthesis almost exactly matched that found in nature.     

新型手性膦-硼烷配合物的合成及其在不对称催化氢化反应中的应用

以苯乙烯为原料,通过Sharpless不对称二羟基化反应合成高对映体纯的苯基乙二醇,经酯化、亲核取代反应转化为手性膦-硼烷配合物.后者克服了有机膦配体易氧化的缺点,其制备过程简单,易于提纯,在空气中可长期保存.该手性膦-硼烷配合物在四氟硼酸-甲醚的存在下解络,生成的自由膦不经分离直接与[Rh(COD)Cl]₂作用生成手性膦-铑原位催化剂.在α-乙酰氨基肉桂酸甲酯的不对称氢化反应中,转化率为100%,对映选择性88%e.e.     

Asymmetric synthesis of the cytotoxic lactone (+)-cardiobutanolide and two novel analogues

A new asymmetric synthesis of the naturally occurring styryl lactone cardiobutanolide and two novel analogues have been achieved starting from d-xylose. The key steps of the synthesis included an initial zinc mediated reductive THF-ring opening, stereoselective olefination and Sharpless asymmetric dihydroxylation. It was shown that cardiobutanolide (1) exhibits promising in vitro antitumour properties against certain human neoplastic cell lines. It was more potent than the commercial anticancer agent doxorubicin against three cell lines (K562, HL-60 and Raji).     

Total synthesis of FR901464: second generation

FR901464, a potent cell cycle inhibitor, was synthesized in a convergent manner using natural chiral pool, l-threonine, ethyl (S)-lactate and 2-deoxy-d-glucose as starting materials.     

Asymmetric synthesis of cytotoxic sponge metabolites R-strongylodiols A and B

The asymmetric synthesis of the marine sponge natural products, R-strongylodiols A 1 and B 2 using a minimum protection strategy is described. The chirality of the natural products was introduced via the Noyori asymmetric reduction of ynones.     

Asymmetric synthesis of aryloxypropanolamines via OsO4-catalyzed asymmetric dihydroxylation

A simple and effective procedure for the enantioselective synthesis of several β-adrenergic blocking agents incorporating the first asymmetric synthesis of celiprolol, is described. The key steps are (i) sharpless asymmetric dihydroxylation of aryl allyl ethers to introduce chirality into the molecules and (ii) conversion of cyclic sulfates into the corresponding epoxides using a three-step procedure.     

Efficient stereodivergent synthesis of 1,4-dideoxy-1,4-iminohexitols from an (S)-glyceraldimine

A stereodivergent synthesis of 1,4-dideoxy-1,4-imino-d-mannitol I and d-allitol III from an (S)-glyceraldimine, which is easily prepared from d-mannitol, has been achieved with overall yields of 62% and 49%, respectively. The synthesis is based on the addition of vinylmagnesium bromide to N-benzylimine 1, derived from readily available (R)-2,3-O-isopropylideneglyceraldehyde, followed by N-allylation or N-acryloylation, ring-closing metathesis and asymmetric dihydroxylation.     

Asymmetric total synthesis of B-ring modified (−)-epicatechin gallate analogues and their modulation of β-lactam resistance in Staphylococcus aureus

Two enantiomerically pure B-ring modified analogues of (−)-epicatechin gallate were synthesised and their modulation of β-lactam resistance using three strains of methicillin resistant Staphylococcus aureus (BB 568, EMRSA-15 and EMRSA-16) evaluated. Sub-inhibitory concentrations (12.5 and 25 mg/L) of the two analogues fully sensitised each of the three MRSA strains to oxacillin, reducing the MIC to less than 0.5 mg/L, identical to levels achieved with ECg. Lower concentrations demonstrated that the position and degree of hydroxylation of the B-ring is important for activity.     

Asymmetric synthesis of furofurans

Furofurans are one of the largest sub-types of classical lignans which have been found to possess a broad range of important biological activities. Tremendous efforts have been directed to develop synthetic methodologies for the synthesis of furofurans, especially in a stereoselective manner, due to their interesting bioactivities associated with the structural and stereochemical complexity. This article summarizes the reports on asymmetric synthesis of furofurans disclosed during the period of 2004–2017.     

Resin-OsO4-金鸡纳生物碱:一种在(E)-二苯乙烯不对称双羟化反应中可循环使用的高效催化剂

用改进的方法把季铵盐共价结合在Merrifield树脂上作为离子交换剂与K2O5O4作用制成Resin—OsO4催化剂，在NaH存在下，以DMF作溶剂，在70℃下奎宁或奎尼丁与1，4-二氯二氮杂萘反应高产率地生成(QN)2PHAL或(QD)2PHAL，Resin—OsO4通过简单过滤可定量回收，回收的催化剂重复使用五次，其活性不变，Resin—OsO4-(QN)2PHAL或(QD)2PHAL催化体系在(E)-二苯乙烯的不对称双羟化反应中的化学产率为84～91％，立体选择性为96-99％ee。     

Asymmetric synthesis of the polyol subunit of the macrolide antibiotic, ossamycin

An asymmetric synthesis of the C1-C16 polyol subunit of the macrolide antibiotic, ossamycin, has been achieved through stepwise carbon-chain elongation reaction from d-glucose.     

Asymmetric synthesis of 3,3-disubstituted isoindolinones

An anionic chiral auxiliary-mediated asymmetric alkylation of carbamate 2 affords 3,3-disubstituted isoindolinones 3 in moderate to high de. The chiral auxiliary can be removed and recovered under mild conditions, and the resulting enantiopure lactams further elaborated.     

Asymmetric synthesis and biological evaluation of 1,3- and 1,4-disubstituted benzo-type lipoxin A4 analogues

The asymmetric synthesis of 1,3 and 1,4-disubstituted aromatic lipoxin A₄ analogues has been accomplished. A total of eight analogues were synthesised in a convergent approach utilising Sharpless asymmetric epoxidation, asymmetric reduction and intermolecular Heck reactions. The set of analogues were assessed for their effect on the production of cytokines IL-12p40, IL-23, IL-6, IL-1β and TNFα. A positive inhibitory result was observed for the production of IL-6 and IL-1β.     

Synthetic studies on C14 cembranoids: synthesis of C4-12 fragment of sarcophytonolides E-G and L and C5-11 fragment of sarcophytonolide L

An efficient stereoselective synthesis of C4-12 fragment of the cembranoids, sarcophytonolides E-G and L and C5-11 fragment of sarcophytonolide L is described. The C4-12 building block is efficiently assembled starting from chiral pool material (R)-carvone employing the Baeyer-Villiger oxidation, modified Knoevenagel condensation and asymmetric dihydroxylation as the key steps. The synthesis of C5-11 fragment is based on orthoester Johnson-Claisen rearrangement as the key step.     

A highly enantioselective synthesis of (−)- and (+)-juglomycin A through Dötz annulation and asymmetric dihydroxylation

A highly enantioselective synthesis of (−)- and (+)-juglomycin A, a quinone antibiotic is described. The synthesis is completed in eight steps, and 19% overall yield and in a high enantioselectivity of 99.5% [for (−)-juglomycin A] and 98.5% [for (+)-juglomycin A]. The synthetic strategy features an efficient combination of the Dötz annulation reaction and asymmetric dihydroxylation as the keys steps.     

Asymmetric synthesis of (3S) 3-benzoyloxymethylisobenzofuranone and its 3R enantiomer as analogues of α,β-butenolides

Both enantiomers of 3-benzoyloxymethylisobenzofuranone have been obtained in good yield in six steps from phthalaldehyde using a d-xylose derivative as a chiral protecting group. The two chiral heterocycles are γ-hydroxymethyl-α,β-butenolide analogues having a benzene ring in positions 2 and 3. The key step was the dihydroxylation using both OsO₄ and AD-mix developed by Sharpless. The asymmetric dihydroxylation using AD-mix required a double diastereoselectivity and gave excellent diastereoisomeric excess.     

Efficient synthesis of beetle aggregation pheromone frontalin and its analogues

(−)-Frontalin is an aggregation pheromone that has found application in selective exterminating of certain harmful insects. This paper discloses an expedite synthesis of (±)-frontalin from a symmetric molecule, 2,6-dimethyl-1,6-heptadiene, in 64% yield. The one-flask operation consists of double dihydroxylation, mono-cleavage, and acid-catalyzed intramolecular acetalation. Our unique strategy was also successfully applied to additional diene substrates such as 4a and 4b.     

新型可回收高聚物负载手性配体在苯乙烯类化合物均相不对称双羟化反应中的催化性能研究

在多聚磷酸和AlCl3存在下，邻苯二甲酸酐与对二氟苯中通过Friedel-Crafts反应环化，以60％的产率生成1，4-二氟蒽醌．在碱性条件下，聚乙二醇单甲醚(HO-OPEG-OMe)与1，4-二氟蒽醌进行亲核单取代反应生成中间体F-AQN-OPEG-OMe，产率88％．然后F-AQN-OPEG-OMe与奎尼丁的锂盐再进行亲核取代反应，以91．7％的产率得到新型手性配体QD-AQN-OPEG-OMe．QD-AQN-OPEG-OMe与OsO4原位配位生成的均相催化剂在4种苯乙烯类化合物的不对称双羟化反应中表现出高的立体选择性(80％～94％ee)和催化活性(产率88％～96％)．催化活性和立体选择性与Sharpless手性配体(DHQD)2AQN相当．反应结束后，加入乙醚可使配体沉淀和回收，配体的回收率均在95％～97％之间．循环使用5次，催化剂的催化活性和立体选择性无明显改变．