Total Syntheses of a Conformationally Locked North‐Type Methanocarba Puromycin Analogue and a Dinucleotide Derivative

Abstract

An original synthetic approach for the first synthesis of an enantiopure methanocarba puromycin (3'-alpha-aminoacylamino-3'-deoxyadenosine) analogue and its cytidine dinucleotide derivative is described. Each compound is conformationally locked in a North-type pucker and exhibits both a pseudoaxial hydroxy group and a pseudoequatorial aminoacyl group. The syntheses were accomplished from D-ribose in 18 and 19 steps, respectively, with key steps being a ring-closing metathesis, a Luche reduction, a Simmons-Smith cyclopropanation, a Mitsunobu coupling, a Mattocks bromoacetylation, a regioselective and a stereoselective nucleophilic substitution, a chemoselective phosphoramidite coupling and a Staudinger-Vilarrasa coupling. Both molecules are being tested for peptidyl transfer efficiency in ribosomes for comparison with the peptidyl transfer kinetics of natural puromycin and other natural and synthetic ribosomal A site substrates.

Efficient, large-scale synthesis and preclinical studies of MRS5698, a highly selective A3 adenosine receptor agonist that protects against chronic neuropathic pain

“…1. The methods used were similar to those reported [20][21][22], except that modifications of the procedures and reagents were introduced in order to adapt the process to a large scale. We have improved upon the synthetic route, showing that MRS5698 could be synthesized on a multi-gram scale from a less expensive starting material, D-ribose 1, instead of L-ribose in the previous method [23].…”

Two Distinct Conformations of GABA Locked by Embedding in the Bicyclo[3.1.0]hexane Core Structure

“…[1][2][3][4][5][6][7][8][9][10][11][12] They have been used as conformationally locked analogues of nucleoside building blocks [9][10][11][12] and as intrinsically interesting building blocks in numerous other applications. [13][14][15][16] They have been reported as intermediates in natural compound synthesis, [17] or as constituents of bioactive compounds, [18,19] novel materials, [20] and catalysts.…”

Practical synthesis of N-(di-n-butylamino)methylene-protected 2-aminopurine riboside phosphoramidite for RNA solid-phase synthesis

“…Our synthetic route to the functionalized 2-aminopurine riboside phosphoramidite 6 starts with the reduction of the commercially available 2-amino-6-chloropurine riboside using Pearlman′s catalyst (Pd(OH) 2 /C) and ammonium formate to yield compound 1 (Scheme 1). The exocyclic 2-amino function was selectively protected by treatment with N,N-dibutylformamide dimethyl acetal (DBFDMA) [25][26][27][28][29] producing nucleoside derivative 2. In the next step, the 5′ and 3′ hydroxyl groups were simultaneously protected by reaction with di-tert-butylsilyl bis(trifluoromethanesulfonate) ((tBu) 2 Si(OTf) 2 ) [30,31], followed by silylation of the 2′-hydroxyl group with tert-butyldimethylsilyl chloride (TBDMSCl) to give compound 3.…”