C-Nucleosides and related compounds. VI. Carbocyclic analogues of C-nucleosides: synthesis and derivatives of some useful intermediates

Abstract

GEORGE JUST, GRANT READER, and BERNADETTE CHALARD-FAURE. Can. J. Chern. 54, 849 (1976).The Diels-Alder adduct of cyclopentadiene and 8-brorno acrylic acid 1 was converted to ~,~-exo-6,7-(dihydroxy-di-O-isopropylidene)-2-hydroxy-3-oxabicyclo[3.2.1]octane (9) in an eight-step sequence and a 24% yield based on 1. Alternatively, the hemiacetal9 was obtained in five steps and 22% yield from norbornadiene through the intermediate lactone 11. The thiosernicarbazone and sernicarbazone of 9 were prepared. The synthesis of the free aldehyde 13 as well as that of the Wittig reaction products 12 and 19 are described. GEORGE JUST, GRANT READER et BERNADETTE CHALARD-FAURE. Can. J. Chern. 54, 849 (1976).La rkction de l'acide 8-bromo acrylique 1 sur le cyclopentadkne conduit au produit d'addition de Diels-Alder correspondant; ce dernier peut Ctre transformi en huit Ctapes avec un rendernent global de 24y0 bask sur 1 en D,L-exo-(dihydroxy-di-0-isopropylidene-6,7 hydroxy-2-oxa-3 bicyclo[3.2.l]octane 9. L'hCmiacCtal 9 a Cgalernent Ct C obtenu en cinq Ctapes avec un rendement de 22'g ? i partir du norbornadikne et en passant par la lactone 11. On d k r i t la preparation de la thiosernicarbazone et de la semicarbazone de 9 ainsi que la synthtse de 1'aldChyde 13 et des produits 12 et 19 provenant de rkctions de Wittig.In a preliminary communication (I), we reported the synthesis of lactol9 and lactone 11. In this paper, we are giving a full account of this work and the description of a second pathway leading to 9 and 11. The syntheses of related derivatives and of the free aldehyde 13 are also described. These compounds are potential intermediates for the preparation of carbocyclic analogues of C-nucleosides.Condensation of 0-bromoacrylic acid 1 with cyclopentadiene in benzene (2) gave the DielsAlder adduct 2 in 75% yield. This compound was almost exclusively the endo carboxylate isomer (3). Treatment of the acid 2 with diazomethane gave, in essentially quantitative yield, the ester 2a which was oxidized to the diol 3 with hydrogen peroxide and a catalytic (4) amount of osmium tetroxide. The diol3, mp 145 "C, was obtained in 50% yield. The stereochemistry of the hydroxy groups in 3 was assigned on the basis of previous work (4, 5) which had shown the preferential exo-hydroxylation of bicyclic[2.2.1] systems of type 2.Attempts to hydroxylate the acid 2 directly were unsuccessful. Crude diol3 was converted to its isopropylidene derivative 3a in 60% yield based on adduct 2. Elimination of hydrogen bromide by treatment of 3a with 1,Sdiazabicyclo[5.4.0]undec-Sene afforded the olefinic ester 4. Upon treatment of diol 3 with acetic anhydride -pyridine, the olefinic diacetate 4a was obtained. Similarly, the olefinic carbonate derivative 4b was the major product from the reaction of diol 3 with phosgene in pyridine. It was not possible to obtain a pure sample of 3a for elemental analysis, although the compound was otherwise well characterized. Attempts at purification by column chromatography, on either silica gel or alumina (activity 1 or...

Carbocyclic nucleosides

“…lo4, 105 Following cis hydroxylation of the corresponding ester 118b with OsO, , the resulting exo diol was protected as the isopropylidene derivative, and after base catalyzed elimination of HBr, the olefin ester 119 was obtained. Ozonolysis, followed by reduction with dimethyl sulfide gave the corresponding ketoaldehyde which was further reduced to the diol 120a.…”

Synthesis and Photophysical Characterization of Aryl-Substituted Polynorbornenediol Acetal and Ketal Multiblock Copolymers

“…The monomer precursor (exo,cis-5norbornene-2,3-diol) was prepared by literature procedures.13 Acetal linkages to aryl ketones and aldehydes were prepared by a modification of a previous literature procedure. 29 General Methods. (A) The aryl methyl ketone or aryl aldehyde (7.9 mmol) was added portionwise to a solution of exo,«s-5-norbornene-2,3-diol13 (7.9 mmol) in 10 mL of CH2C12 under N2.…”

Carbocyclic Nucleoside Analogs. 1. Concise Enantioselective Synthesis of Functionalized Cyclopentanes and Formal Total Synthesis of Aristeromycin

“…Although protection of 12 as an acetonide has previously been reported, the acid sensitivity of the isopropylidene made it an unsuitable protecting group for our purposes . Intermediates available directly from acetonide protected 12 could not be successfully converted to the tri- O -benzyl ether 16 .…”