立体选择性环氧醇还原重排反应研究-环状化合物1,3-二醇的新合成方法

路易斯酸催化下的环氧醇开环重排反应是极为重要的一类反应[1～3], 但是, 至目前所发现的反应都限于控制2个立体中心. 我们在前文[4]中报道了几个环氧醇在异丙醇铝(AIP)的作用下生成1,3-二醇的例子. 最近我们合成了一系列不同结构的底物, 对该反应进行了系统深入的研究, 得出了一些规律性的结果, 即在某些情况下能控制3个立体中心, 别的情况下至少能控制2个立体中心. 该反应还建立了一个立体控制的季碳中心. 我们认为该反应是一个极好的合成手性1,3-二醇特别是螺环二醇的新方法, 对于研究新的不对称反应催化剂具有重要的理论和应用价值[5], 本文对这一反应的初步结果进行了讨论.     

Stereoselective synthesis of the C1-C10 fragment of rhizoxin D

A novel approach towards the synthesis of the C1-C10 fragment of the biologically active antimitotic agent rhizoxin D is described. The synthesis involves a stereoselective Michael addition reaction of lithium diallyl cuprate with an α,β-unsaturated six membered lactone.     

Stereoselective synthesis of peracetylated (−)-gloeosporiol via acid catalysed intramolecular etherification

A simple and an efficient strategy have been developed for the stereoselective synthesis of peracetylated (?)-gloeosporiol by acid catalysed cyclisation from the commercially available starting materials.     

A novel and highly stereoselective route for the synthesis of non-racemic 3-substituted isoindolin-1-one targets

A new, versatile and highly stereoselective approach for the synthesis of non-racemic 3-substituted isoindolin-1-ones is described from a readily available chiral template. The potential of this new protocol is demonstrated through the synthesis of an enantiomerically enriched 3-alkyl N-H isoindolin-1-one target with an e.e. of 98%.     

L-苏式二氢鞘氨醇的立体选择性合成

二氢鞘氨醇（ＤＨＳ）是２－氨基－１，３－二羟基的饱和长链氨基醇化合物，是构成鞘脂类（包括鞘磷脂和糖鞘脂）的主链部分．由于鞘脂类在自然界中来源稀少，又很难得到纯品．因此，作为鞘脂类主链部分的二氢鞘氨醇的合成有重要的意义［１］．二氢鞘氨醇有两个手性碳，共...     

Alkynes to (E)-enolates using tandem catalysis: stereoselective anti-aldol and syn-[3,3]-rearrangement reactions

A new tandem catalysis strategy that transforms alkyne derivatives to (E)-enol-equivalents followed by stereoselective anti-selective aldol coupling or syn-selective [3,3]-rearrangement transformations is reported. The mechanism is thought to proceed through an interchanging series of Lewis acid and Brønsted acid catalyzed reactions via the intermediacy of a ketiminum ion species.     

2-Isopropylbenzimidazole and 2-methylbenzimidazole as bulky proton sources: Stereoselective protonation and application to the synthesis of γ- and δ-lactones

2-Isopropylbenzimidazole and 2-methylbenzimidazole have been found to be effective bulky proton sources for stereoselective protonation of chiral enolate anions. 2-Isopropylbenzimidazole worked in the stereoselective protonation of the Birch reduction of chiral α,β-unsaturated imides. On the other hand, 2-methylbenzimidazole was found to be the best protonation reagent in the isomerization reaction of α,β-unsaturated imide into β,γ-unsaturated imide. The Birch reduction using 2-isopropylbenzimidazole realized a concise and stereoselective synthesis of δ-lactone 14, a sex pheromone of Macrocentrus grandii, while the isomerization reaction using 2-methylbenzimidazole was employed in the highly stereoselective synthesis of the γ-lactone intermediate in the synthesis of depsipeptide antibiotics. These bulky proton sources would be powerful tools to achieve a concise synthesis of natural products.     

Short and stereoselective synthesis of manzacidins A and C, and their enantiomers

A short and stereoselective synthesis of manzacidins A and C, and their enantiomers was achieved via stereoselective hydrogenation reactions of dehydroamino acid esters 5-8 using a chiral Rh catalyst.     

Synthesis of the C9-C21 fragment of debromoaplysiatoxin and oscillatoxins A and D

A highly stereoselective synthesis of the C9-C21 fragment of debromoaplysiatoxin and oscillatoxins A and D has been devised. This new approach relies on the cross coupling of titanium enolates from N-acyl-1,3-thiazolidine-2-thiones and dialkyl acetals and the selective hydrogenolysis of O-benzyl protecting groups.     

Stereoselective synthesis of the right-hand cores of 16-methylated oxazolomycins

The right-hand heterocyclic cores of oxazolomycins having either 16R or 16S-methyl group configurations on the β-lactones were stereoselectively synthesized from the common intermediate utilized for our previous syntheses of neooxazolomycin and oxazolomycin A. In addition, the right-hand segment required for the synthesis of KSM-2690 and lajollamycin members was also synthesized in a stereoselective manner.     

The efficient synthesis of (3R,4R,5R)-3-amino-4,5-dimethyl-octanoic acid, a chiral β-amino acid with potent affinity for the α2δ protein

A chiral β-amino acid containing three contiguous chiral centers was synthesized efficiently in 11 steps, employing enantio-enriched β-ketoester as a key intermediate, via stereoselective catalytic hydrogenation of the corresponding enamide. Stereoselective 1,4-addition of a methyl group and protonation were key to the preparation of the desired acid 12. Mild and efficient reaction conditions were applied to the enamine formation and protection to avoid epimerization at C-4 of compounds 13 and 14. The final compound was found to display potent affinity for the α₂δ-protein that is a recognized drug target for the treatment of a variety of diseases.     

Effects of ring substituents on enantioselective recognition of amino alcohols and acids in uryl-based binol receptors

The uryl-based binol aldehyde, (S)-2-hydroxy-2′-(3-phenyluryl-benzyl)-1,1′-binaphthyl-3-carboxaldehyde (1), binds 1,2-amino alcohols and amino acids stereoselectively by reversible formation of imine bond. Hydrogen bond (between uryl group and alcohol -OH moiety) plays an important role in the stereoselectivity of amino alcohols. Hence, any substituents on phenyl group in 1 are expected to affect H-bond ability of uryl group. To study the effects of ring substituents on the stereoselective recognition of amino alcohols, (substituted phenyl)uryl-based chiral binol receptors have been prepared. The receptors with electron-donating X substituents have been synthesized from (S)-2-methoxymethoxy-2′-hydroxy-1,1′-binaphthyl-3-carboxaldehyde and X-phenyluryl-benzyl bromide. The receptors with electron-withdrawing Y substituents, however, required a different synthetic strategy including transformation of an aldehyde to alcohol. The incorporation of the electron withdrawing groups slightly accelerated the stereoselective recognition property of the receptor. Though the acceleration is not so remarkable, this work demonstrates the versatile derivatization of 1 in achieving higher stereoselective recognition of 1,2-amino alcohols and stereoconversion of l-amino acids to d-amino acids.     

Synthesis of Gymnasterone B, an antitumor steroid from Gymnascella dankaliensis

A stereoselective approach toward a marine natural product, Gymnasterone B, has been achieved via a series reaction from cholic acid.     

Highly stereoselective Michael reduction/intramolecular Michael reaction cascade to synthesize trans-stereodiad comprising an all-carbon quaternary stereogenic center

A highly stereoselective Michael reduction/intramolecular Michael reaction cascade is described. The cascade is initiated by the regioselective Michael reduction of an α-methylidene ester with L-Selectride. This is followed by the highly stereoselective intramolecular Michael reaction which efficiently constructs a six-membered carbocyclic ring with formation of the trans-stereodiad, composed of an all-carbon quaternary center and a tertiary stereogenic center. The stereoselectivity is perfectly controlled by the choice of alkene geometry in the Michael acceptor.     

Short diastereoselective synthesis of cis- and trans-hexahydropyrido[2,1-a]isoindole derivatives

A new and highly stereoselective access to 4,10b-trans or 4,10b-cis hexahydropyrido[2,1-a]isoindole derivatives is reported, both requiring an intramolecular Mannich-type reaction as key step. The cis diastereoisomer is obtained in three steps from a 2-alkyl benzaldehyde through the stereoselective formation of a 2,6-cis-disubstituted piperidine, while the trans stereomer is efficiently obtained, in a single step, if a 2-formyl benzoic acid is involved in the Mannich cyclization process.     

Synthetic studies on neomarinone: practical and efficient stereoselective synthesis of the side chain

A practical and efficient stereoselective synthesis of the side chain of neomarinone is reported. The synthesis was achieved in six steps (41% overall yield) from 2-methyl-2-cyclohexenone. The key step is a novel stereoselective 1,4-conjugate addition/enolate alkylation by an epoxide-opening reaction.     

Untersuchungen zur Synthese des Nodusmicin,I: Darstellung von (±)-(1R*,5R*,6R*,7S*8R*,9R*,10R*)-5-Acetyl-7,9-dibenzyloxy-10-hydroxy-8-methylbicyclo[4.4.0]decan-3-on

Summary Our first target on the way towards the synthesis of nodusmicin is the preparation of the title compound. Meso diol1 is partially etherified, then oxidized to the enone. The sterically compressed structure of this compound is the rationale of the highly stereoselective introduction of the substituents. (CH₃)₂CuLi introduces the methyl group and the enolate is captured as silylenol ether, which in turn is transformed to the -hydroxyketone by OsO₄. Reduction leads to the vicinaltrans diol. Protection of theexo-hydroxy group is followed by treatment with sodium in ethanol. Via intramolecular nucleophilic addition, substitution and dechlorination the tetracyclic diketal8 is formed. After exchange of the protective groups and partial hydrolysis of the ketals the tertiary alkohol is obtained with methyl Grignard reagent. Acidic fragmentation yields the desired title compound.

     

Stereoselective synthesis of enantiopure N-protected-3-arylpiperazines from keto-esters

An efficient method for a stereoselective synthesis of optically pure N-Boc-3-arylpiperazines has been developed. After optimization of the protecting group strategy and experimental conditions, compounds were obtained via a highly stereoselective synthesis in up to 45% overall yield. This is a practical route to optically pure piperazines for medicinal chemistry.     

A flexible method for the synthesis of 2-substituted 1,2,5,6-tetrahydropyridines and piperidines from chloro-containing propargylamines

A general approach for the stereoselective synthesis of 2-substituted 1,2,5,6-tetrahydropyridines and piperidines is described. The addition of 4-chloro-1-butyne to Ellman sulfinimines to produce chloro-containing propargylamines, reduction with Lindlar catalyst, and cyclization using LHMDS provides efficient, stereoselective access to diverse 2-substituted 1,2,5,6-tetrahydropyridines. For substrates incompatible with the LHMDS cyclization reaction conditions removal of the sulfinamide moiety and cyclization with Cs₂CO₃ allows the preparation of the corresponding 2-substituted 1,2,5,6-tetrahydropyridines. This method can be extended to the synthesis of 2-substituted piperidines through reduction of the chloro-containing propargylamine with PtO₂.     

A cross-metathesis approach for the synthesis of tedanolide and 13-deoxytedanolide: stereoselective synthesis of the C3-C16 segment

A unified synthetic strategy has been devised for the synthesis of both tedanolide and 13-deoxytedanolide, which involves a cross-metathesis reaction as the key step. We report herein the stereoselective synthesis of the C3-C16 segment (+)-5b and subsequent manipulation of the C12-C13 double bond leading to the preparation of both tedanolides.