Synthesis and ring-opening reactions of functionalized sultines. New approach to sparsomycin

Abstract

An efficient route leading to the functionalized five-membered cyclic sulfinate esters (y-sultines) 14a,b and 21a,b is described on the basis of the reaction of the N-protected cystinol derivatives 11 and 20, respectively, with N-chlorosuccinimide (NCS) and AcOH. Ring-opening reactions of the sultines can be performed in two ways. Treatment of 14 with Clz or NCS/HCl gives the sulfonyl chloride 15 by cleavage of the C-O bond. Selective cleavage of the S-OR bond occurs when 14 or 21 is treated with MeSCH2Li, n-BuLi, or C,H,C(Li)(H)CN to yield the hydroxyalkyl sulfoxides 22-26. These nucleophilic ring-opening reactions are stereospecific and proceed with inversion at the sulfoxide sulfur atom. The synthesis of 23a constitutes a new approach to the antibiotic sparsomycin (1). Circular dichroism measurements can be employed in the assignment of absolute configurations to the sulfoxide sulfur atom of the sultines 14a,b and 21a,b (patents pending).

Sparsomycin–Linezolid Conjugates Can Promote Ribosomal Translocation

“…Synthesis: The syntheses of compounds 1-14 either were performed as reported [45][46][47] or are described in the Supporting Information.…”

Five‐Membered Heterocycles with Two Heteroatoms: O and S Derivatives

“…Nucleophilic attack on the cysteine-derived chiral 4-amino-1,2-oxathiolane 2-oxide 298 by alkyllithiums takes place on the sulfur atom with inversion of configuration to give 299 (Scheme 11.98) [245].…”

“…Figure 11.2 Geometry of a 1,2-oxathiolone derivative. Oxathiolane 277 is prepared by treatment of N-alkylcystinol 276 with NCS or NBS (Scheme 11.87) [233]. Substituted 1,3-thioalcohols 278 can also be oxidized with NaIO 4 to give the corresponding 1,2-oxathiolane-2-oxides 279 (Scheme 11.88) [234].…”

Synthesis and Activity of Pyrimidinylpropenamide Antibiotics: The Alkyl Analogues of Sparsomycin

“…[7][8][9][10] These potentially important biological activities have made 3 an attractive target for a potential antineoplastic compound. 11) Since thê rst synthetic study of sparsomycin in 1976, 12) synthetic studies of sparsomycin, [13][14][15] total synthesis, [16][17][18] biosynthesis, 19,20) and structure-activity relationship studies [21][22][23][24][25][26][27] have been widely reported. There have been many reports on the antitumor, antibacterial, antifungal, and antiviral properties; however, normalization of the phenotype of oncogene-transformed cells by 3 and its analogues has not previously been reported.…”