Total and stereospecific synthesis of 2′-deoxycadeguomycin

Abstract

An efficient and stereospecific synthesis of 2'-deoxycadeguomycin (3) from the novel 7-deazapurine derivatives 2-amino-4-chloropyrrolo[2,3-dJpyrimidine-5-carbonitrile (10) or methyl 2-amino-4-chloropyrrolo[2,3-dJpyrimidine-5-carboxylate (12) has been accomplished.Cadeguomycin (1) is a novel nucleoside antibiotic isolated recently' from the culture broth of Streptomyces hygroscopicus IM7912T as a minor component together with tubercidin (4), and characterized as 2-amino-4-0~0-3,4-dihydro-7-P-~ribofuranosylpyrrolo[2,3-d]pyrimidine-5-carboxylic acid.2 This nucleoside inhibited the growth of solid IMC carcinoma and pulmonary metastasis of Lewis lung carcinoma in mice with appreciably low toxicity.' It also enhanced cell-mediated immunity and macrophage activity.' Cadeguomycin displayed a unique property of enhancing uptake of pyrimidine nucleosides into K562 human myelogenous leukaemic cells and YAC-1 murine lymphoma cells, and it potentiated cytotoxicity of ara-Q-5 as well as 5-fluoro-2'-deoxycytidineh both in vitro and in vivo. This interesting and potent activity, coupled with its biogenetic relationship with guanosine, resulted in the mu1 tistep syntheses of cadeguomycin7-~ and ara-cadeguomycin (2) .lo However, the synthesis of 2'-deoxycadeguomycin (3) has not yet been realized. We now report the first stereospecific and total synthesis of (3) from the hitherto inaccessible agl ycones 2-amino-4-chloropyrrolo[ 2,3-d]pyrimidine-5-carbonitrile (10) or methyl 2-amino-4-chloropyrrolo[2,3-d]pyrimidine-5-carboxylate (12).Our approach was to build the substituted pyrrole ring onto

Progress in 7-Deazapurine - Pyrrolo[2,3-d]pyrimidine - Ribonucleoside Synthesis

“…Since then, the 7deazapurine 2'-deoxyribonucleosides could be prepared in a stereo-controlled manner, with the exclusive formation of β-D-2'-deoxyribonucleosides [25,26]. Later on, this protocol was applied to the synthesis of other base-modified 2'deoxyribonucleosides [25,[28][29][30] as well as to 7-deazapurine ribonucleosides [31][32][33][34][35]. This was of particular value because the common glycosylation methods developed for purine nucleosides can not be applied efficiently to the synthesis of the corresponding 7-deazapurine nucleosides.…”

Synthesis of 5‐[(4‐phenylpiperazin‐1‐yl)methyl]pyrrolo‐[2,3‐d]pyrimidine derivatives as potential dopamine D4 receptor ligands

“…Amongst others this methodology [19][20][21] was applied to synthesize the multi-targeted antifolate Pemetrexed [22]. In the range of this reaction other working groups have observed the formation of interesting by-products [21,[23][24][25]. Already 1978 Secrist et al had found out that besides the pyrrolo [2,3d]pyrimidin-4-one derivative a furo[2,3-d]pyrimidine-2,4diamine was formed [21].…”

Advances in the Synthesis of 7-Deazapurine - Pyrrolo[2,3-d]pyrimidine 2-Deoxyribonucleosides Including D- and L-Enantiomers, Fluoro Derivatives and 2,3-Dideoxyribonucleosides

“…In 1984 Robins and Kazimierczuk used NaH to generate the nucleobase anion with MeCN as solvent and employed the sugar halide 6 in the glycosylation reaction [33]. This method was applied to the synthesis of a number of 7-dezapurine 2'-deoxyribonucleosides, such as 7-deaza-2'-deoxyguanosine (11a), its derivatives 11d, 11g, 11h, 11j [84][85][86][87], and related to 2'-deoxytubercidin derivatives 13a, 13f, 13j, 17f, 20, 37a, and 60-66 (Scheme 28) [33,34,[88][89][90].…”

“…The synthesis of 2'-deoxycadeguomycin made by the sodium salt procedure is shown in Scheme 33 [85,93] which was converted to 7-nitro-7-deazapurine 87. Compound 87 was glycosylated with 2-deoxy-3,5-di-O-(p-chlorobenzoyl)--D-erythro-pentofuranosyl chloride (88) in DMF in the presence of NaH resulting in -D-nucleoside 89.…”