Syntheses of C-nucleosides. IX. Reactions of D,L-3,4-di-O-isopropylidene-2,5-anhydroallose with Wittig reagents. Syntheses of bis-homo anhydro-C-nucleosides.

Abstract

GEORGE .IUST, MOHABIR RAMJEESINGH, and TENG JIAM LIAK. Can. J. Chem. 54, 2940Chem. 54, (1976. The nrnr spectra of the two anomers of 1-0-acetyl-3,4-di-0-isopropylidene-2,s-anhydro-D, L-allose (2a, 26) are discussed. The reactions of D,L-3,4-di-0-isopropylidene-2,s-anhydroallose (1) with carbethoxymethylenetriphenylphosphorane, bromocarbethoxymethylenetriphenylphosphorane and ethyl triphenylphosphoranylidene pyruvate to give respectively the olefin derivatives 7, 9, and 10 and an internal Michael addition product 11 are described. From 11, two bis-homo anhydro-C-nucleosides having 6-azauracil (15) and 4-hydroxy-5-carboxarnidopyrazole (19) bases were synthesized. GEORGE JUST, MOHABIR RAMJEESINGH, et TENG JIAM LIAK. Can. J. Chem. 54, 2940Chem. 54, (1976. Les spectres rmn des deux anomkres du 0-acktyl-1 di-0-isopropylidene-3,4 anhydro-2,s D,L-allose (2a, 2b) sont rapport& et discutks. On dhrit aussi les rkactions du di-0-isopropylidkne-3,4 anhydro-2,5 D,L-allose avec le carbCthoxymkthylene triphenylphosphoranne, le bromocarbkthoxymkthylene triphCnylphosphoranne et le triphknylphosphorannylidene pyruvate d'kthyle donnant respectivement les dkrivks olkfiniques 7, 9, 10 et le produit de condensation interne de Michael 11. A partir du compose 11, on a synthCtisC deux bis-homo anhydro-CnuclCosides ayant les bases aza-6 uracile 15 et hydroxy-4 carboxamidopyrazole-5 19.In previous papers (l,2), we reported a synthesis of ~,~-3,4-di-O-i~0pr0pylidene-2,5-anhydroallose (1) and its use for C-nucleoside syntheses. In this paper we wish to present a study of the reactions of D,L-3,4-di-0-isopropylidene-2,5-anhydroallose with Wittig reagents and the syntheses of two bis-homo anhydro-C-nucleosides.In our synthesis of D,L-3,4-di-0-isopropylidene-2,5-anhydroallose, both the a and / 3 anomers were obtained in approximately equal amounts. This conclusion was based on their nmr spectral data in which the anomeric protons of both anomers have different chemical shifts. They appeared at 5.08 and 5.21 ppm and their approximate intensity was half a proton each.It was possible to separate the a and / 3 forms of the acetate derivative (2a, 2b) by thin layer chromatography eluting with ether-hexane (1 :2). The two anomers with Rf = 0.45, mp 64.5-65.6"C, and R, = 0.4, mp 140.5-141.5 "C, had virtually identical infrared and mass spectra but different nmr spectra. Structural assignment of the two anomers were based on their nmr data. Generally for sugars, an equatorial anomeric proton produces a signal at lower field by approximately 25 Hz than an axial proton (3). On this basis, the anomer (Rf = 0.45) with the Can. J. Chem. Downloaded from www.nrcresearchpress.com by 52.36.4.81 on 05/12/18For personal use only.

Chemistry of α-Oxoesters: A Powerful Tool for the Synthesis of Heterocycles

“…By condensation of the isomeric mixture 203a and 203b with ethyl hydrazinoacetate hydrochloride, corresponding isomeric hydrazones 204 were obtained, which underwent Dieckmann cyclization to furnish an isomeric mixture of 4-hydroxy pyrazole derivatives 205, when treated with NaOMe in MeOH under reflux conditions for 3 h (Scheme 57). 115 Similar Dieckmann condensation of α-ketoester 2-carboalkoxymethylhydrazones was reported by Farkašet al 116 ]-s-indacen-9-one 206 with diethyl oxalate in the presence of NaOEt in benzene at room temperature (Scheme 58a). 117a Similar methodology was used to synthesize pyrazole-3-carboxylates 210 fused to thiopyrane ring by condensation of corresponding oxo-glyoxalate 209 with hydrazine derivatives in AcOH under reflux conditions (Scheme 58b).…”

“…By condensation of the isomeric mixture 203a and 203b with ethyl hydrazinoacetate hydrochloride, corresponding isomeric hydrazones 204 were obtained, which underwent Dieckmann cyclization to furnish an isomeric mixture of 4-hydroxy pyrazole derivatives 205, when treated with NaOMe in MeOH under reflux conditions for 3 h (Scheme 57). 115 Similar Dieckmann condensation of αketoester 2-carboalkoxymethylhydrazones was reported by Farkašet al 116 By reaction of N-benzylpiperidin-4-ones with diethyl oxalate mediated with NaOEt in EtOH at −10 °C, then warmed to room temperature, corresponding Claisen products were in situ generated, which in treatment with hydrazine hydrate (1.1 equiv) and AcOH (3 equiv) transformed into unexpected tetrahydropyrazolo[1,5-c]pyrimidines 215. In the proposed reaction mechanism, hydrazone 211 cyclized to tautomer of pyrazole 212 (213), which underwent retro-Mannich reaction that resulted in the formation of iminium ion 214 along with ring opening, followed by cyclization to 215, by addition of nitrogen of pyrazole to iminium ion 214.…”

“…The reaction of the 2,5-anhydroallose 201 with ethyl triphenylphosphoranylidene pyruvate at 90 °C for 2 days gave both diastereoisomers 203 via internal Michael addition of α,β-unsaturated α-ketoester 202 . By condensation of the isomeric mixture 203a and 203b with ethyl hydrazinoacetate hydrochloride, corresponding isomeric hydrazones 204 were obtained, which underwent Dieckmann cyclization to furnish an isomeric mixture of 4-hydroxy pyrazole derivatives 205 , when treated with NaOMe in MeOH under reflux conditions for 3 h (Scheme ) . Similar Dieckmann condensation of α-ketoester 2-carboalkoxymethylhydrazones was reported by Farkaš et al to synthesize corresponding 3-substituted 4-hydroxypyrezole-5-carboxylates in 39–85% yields.…”