含手性磷酸酯基的寡核苷酸类似物的立体控制性合成

本文总结了近十几年来立体控制性合成含手性磷酸酯基的寡核苷酸类似物的进展, 重点介绍了寡核苷酸硫代磷酸酯和甲基膦酸酯的立体控制性合成方法 .     

New stable neutral radical with intramolecular hydrogen bonding: synthesis and characterization of 2,5,8-tri-tert-butyl-7-hydroxy-6-oxophenalenoxyl

A new stable neutral radical with intramolecular hydrogen bonding, 2,5,8-tri-tert-butyl-7-hydroxy-6-oxophenalenoxyl, was synthesized from the corresponding dihydroxyphenalenone and isolated as a stable solid under air atmosphere at room temperature. The structure was unequivocally determined by means of IR spectra, ESR/ENDOR techniques, and DFT calculations.     

Stereocontrolled syntheses of alpha-C-mannosyltryptophan and its analogues

The total synthesis of alpha-C-mannosyltryptophan (C-Man-Trp), a naturally occurring C-glycosylamino acid, was achieved from a commercially available alpha-methyl-D-mannoside in 10 steps including the following key steps: the C-glycosidation of a mannose derivative with a stannylacetylene, Castro indole synthesis, and Sc(ClO4)3-promoted coupling with L-serine-derived aziridine carboxylate. The glucose- and galactose-analogues of C-Man-Trp were also synthesized in a similar manner. Conformational analyses of the synthesized C-glycosyltryptophan and its synthetic intermediate are briefly discussed.     

Stereocontrolled synthesis of enantiomerically pure unsaturated analogues of 2,6-DAP. Part 5

An efficient new stereocontrolled synthesis of (2R,6R)-(+)- and (2S,6S)-(−)-2,6-diamino-4-methylene-1,7-heptanedioic acid 8a and 9a, respectively, has been accomplished starting from the glycine-derived chiral synthon 1. The enantiomerically pure α-alkyl derivatives 8b–d and 9b–d have also been synthesized. The absolute configuration of the new stereocenters was assigned on the basis of ¹H NMR spectra.     

Stereocontrolled synthesis of novel 6′(α)-hydroxy carbovir analogues

This paper describes the racemic and stereoselective synthetic route for a novel 6′(α)-hydroxy-carbovir from a simple acyclic precursor, Solketal. The relative stereochemistry of the target nucleosides was successfully controlled by a sequential stereoselective glycolate Claisen rearrangement followed by a ring-closing metathesis (RCM). Adenine and cytosine were coupled using a Pd(0) catalyzed allylic alkylation strategy in a high regio- and stereoselective manner.     

Stereocontrolled synthesis of 2-alkenyl-4-methylene tetrahydropyrans

A variety of 2-alkenyl-4-methylene tetrahydropyrans were synthesized via consecutive transition metal-catalyzed bond forming processes. In this approach, ruthenium-catalyzed coupling of homoallylic carbonates and homopropargylic alcohols generates substrates containing the requisite functionality for a palladium-mediated cyclization, thereby providing concise access to the target structures. The installation of a trisubstituted alkene at the C-2 position was achieved using an olefin cross metathesis process.     

Stereocontrolled synthesis of onchidins

[structure: see text] The first total synthesis of a molecule possessing the stereochemistry proposed for onchidin is described. The structure synthesized appears to be different from that of the marine natural product.     

Stereocontrolled synthesis of dihydropseudoclovene-B

Aryl participated intramolecular cyclisation of the bromophenol 16 yielded the dienone 17 which was converted into dihydropseudoclovene-B (7) via a stereocontrolled route.     

1,3-Dipolar cycloaddition reaction of D-glucose-derived nitrone with allyl alcohol: synthesis of 2-hydroxy-1-deoxycastanospermine analogues

[reaction: see text] The synthesis and evaluation of glycosidase inhibitory activity of polyhydroxylated indolizidine alkaloids namely 2-hydroxy-1-deoxycastanospermine 3a,b and 2-hydroxy-1-deoxy-8a-epi-castanospermine 3c,d is reported. The key step involves the intermolecular 1,3-dipolar cycloaddition of allyl alcohol to d-glucose-derived nitrone 4, followed by tosylation, that afforded four diastereomeric sugar-substituted isoxazolidines 5a-d with the desired regioselectivity. The one-pot conversion of 5a-d to pyrrolidines 8a-d by hydrogenolysis, removal of 1,2-acetonoide functionality, and hydrogenation afforded corresponding target molecules 3a-d.     

Stereocontrolled synthesis of quinine and quinidine

Disubstituted cyclopentene was prepared from cyclopentene monoacetate and transferred into disubstituted piperidine via oxidative cleavage of the olefin moiety followed by piperidine ring formation. The piperidine was then condensed at the side chain with a quinoline part to afford the olefin precursor of quinine. Finally, the olefin was converted into quinine through the corresponding epoxide. Quinidine was synthesized in a similar way.     

Stereocontrolled synthesis of (+)-boronolide

Boronolide was synthesized stereoselectively from hydroxyacetylfuran 5 and valeraldehyde 6 using a novel dizinc aldol catalyst. Ring closing metathesis provides the lactone ring. The synthesis requires 12 steps and proceeds in 26% overall yield. [reaction: see text]     

Stereocontrolled synthesis of lepadiformine A

In this paper we present results of a study into whether the tricyclic core of the lepadiformines A-C can be accessed via intramolecular hetero-Diels-Alder cycloaddition. We are able to demonstrate that such a process is possible and that the reaction proceeds in an endo-selective fashion, providing the correct relative stereochemistry for this family of natural products. By employing this approach we have been able to develop a short (7 step) synthesis of (+/-)-lepadiformine A, starting from commercially-available trans-2-nonenal.     

Stereocontrolled synthesis of beta-difluoromethylated materials

Investigation of synthetic routes for regio- and stereocontrolled fluorinated materials with a difluoromethyl group, using ethyl bromodifluoroacetate as a starting material, is described. In particular, (E)-difluoromethylated trisubstituted olefins were prepared via the proton migration reaction catalyzed by using fluoride anion. Further, optically active beta-difluoromethyl esters were obtained by the enzymatic resolution.     

Stereocontrolled total synthesis of pancratistatin

A new total synthesis of the antitumor alkaloids, pancratistatin (1), has been accomplished from readily available staring materials. The Claisen rearrangement of dihydropyranethylene 5 was employed to construct the A and C rings. Stereo- and regiocontrolled functional group interchange, such as iodolactonization, dihydroxylations, and a cyclic sulfate elimination reaction, allows for the production of the target natural product. [reaction: see text]     

Peptide synthesis with benzisoxazolium salts—III : Utility of 7-hydroxy-2-ethylbenzisoxazolium fluoroborate in the synthesis of peptides

The scope and limitations of the 7-hydroxy-2-ethylbenzisoxazolium salt method of forming amide bonds are outlined through the synthesis of a variety of simple peptide derivatives containing all of the common amino acids with the exceptions of arginine and histidine. The 3-acyloxy-2-hydroxy-N-ethylbenzamides derived from C-terminal serine or threonine containing peptides are found to react with amines at anomalously slow rates and with the formation of transesterified byproducts; a mechanistic explanation is offered. The utility of the method for the synthesis of medium sized peptides is examined by synthesis of oligomers of Gly-L-Leu-Gly.     

Stereocontrolled synthesis of the enantiomers of 1-[2-hydroxy-3-(4-phenyl-1-piperazinyl)-propyl]-pyrrolidin-2-one

The asymmetric synthesis of 1-[2-hydroxy-3-(4-phenyl-1-piperazinyl)-propyl]-pyrrolidin-2-one 1 is described. Enantiomers of compound 1 were obtained using the Sharpless asymmetric dihydroxylation (AD) or hydrolytic kinetic resolution (HKR) methods. The enantiomers of compound 1, which were obtained by HKR had higher enantiomeric excesses than those which were synthesized by AD and epoxidation. The enantiomeric purity of the synthesized compounds was determinated by capillary electrophoresis.