Synthesis of S-deoxo- (R) -sparsomycin

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

“…Fuji Silica Chemical Ltd. BW-300 silica gel was used for column chromatography. (12). An oven-dried, 300-ml three-necked ‰ask equipped with a septum and a nitrogen inlet was charged with Ti(Oi-Pr)4 (0.63 g, 2.2 mmol), (R)-(＋)-1,1?-bi-2-naphthol (1.25 g, 4.4 mmol) and carbontetrachloride (50 ml).…”

“…[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.…”

Sparsomycin – a Review and Re-assessment

“…Figure 2. Structures of selected sulfoxide-containing pharmaceutical agents and S-deoxy-L-sparsomycin (11) Preliminary synthetic studies [33][34][35][36] had afforded S-deoxy-L-sparsomycin (11) and related derivatives, 33 as a prelude to analog exploration for the structure activity relationship studies. Continuing interest in the biological effects of the alkaloid attracted further synthetic approaches to 1 and eventually its diastereoisomers.…”

“…38 Further approaches were developed by Ottenheijm et al to generate the uracil acrylic acid moiety 13 and an appropriate amino acid-derived fragment. 11,36 The preferred route to 13 continued to involve the aldehyde 24 11 in a Wittig reaction with (C6H5)3P=CHCO2Et and base hydrolysis. Four potential routes for the transformation of the cysteine thiol group were considered, one involved developing the dithioacetal unit followed by regioselective oxidation.…”

“…39 The elaborate first attempt effectively inverted C-2 of 14 but was deemed too complex for large scale studies. The strategy in the second pathway was to switch the functionalities of the C-2 carbons, thereby inverting the chiral center from R to S. The route commenced with L-serine (36) which was triply protected to afford 37. Reduction of the methyl ester, tosylation, and thiomethylation produced the methyl sulfide 38.…”