Highly Stereoselective Synthesis of the Anti-Platelet Activating Factor, 4-Thiazolidinones, Using Silyl Derivatives of 2-Mercaptoalkanoic Acids

Abstract

The cyclo-condensation of silyl 2-mercaptoalkanoates and arylmethyleneamines proceeded with high stereoselectivity to give alternatively both the cis- and trans-2,5-disubstituted 4-thiazolidinones, some of which are known as anti-platelet activating factor-active drugs. The use of the piperidine catalyst and no catalyst showed very high cis-stereoselectivity (cis/trans = 10/1—50/1) during the reaction. On the other hand, the trans-selective reaction was promoted by Ti(O-i-Bu)4 and Al(O-s-Bu)3 catalysts (cis/trans = 1/8—1/25). Both reactions were conducted with higher cis- and trans-selectivities as compared with those of the alkyl 2-mercaptoalkanoates under mild conditions. The cyclo-condensation using trimethylsilyl 2-(trimethylsilylthio)propionate and methyl 2-(trialkylsilylthio)propionates proceeded by the action of a catalytic amount (0.02 molar amount) of tetrabutylammonium fluoride with moderate cis-selectivity.

Thiazoles and Thiazolidinones as COX/LOX Inhibitors

“…Thiazolidinones, on the other hand, are derivatives of thiazolidine, a saturated form of thiazole, with a carbonyl group at position 2, 4, or 5. The chemistry of thiazolidinones has drawn scientific interest through the years because this particular ring system is the core structure in a variety of synthetic compounds with a broad spectrum of biological activities, such as antimycobacterial [ 41 , 42 ], antifungal [ 43 , 44 , 45 , 46 ], anti-cancer [ 47 , 48 , 49 , 50 ], anticonvulsant [ 51 , 52 , 53 ], anti-edematous [ 54 ], antidiarrheal [ 55 ], anti-HIV [ 56 , 57 ], anti-platelet-activating factor [ 58 ], antidiabetic [ 59 ], antihistaminic [ 60 ], anti-inflammatory [ 61 , 62 , 63 ], analgesic [ 64 , 65 ], antimicrobial [ 66 , 67 , 68 , 69 ], antidepressant [ 70 ], etc.…”

Titanium Reagents for the Synthesis of 2-Substituted Benzo[b]thiophenes on the Solid Phase

“…We realized that tert -butyldimethylsilyl protection of the thiol might be more effective because although S−Si bonds would be cleaved easily under acidic conditions, the functionality should be stable to low-valent titanium complexes as the silicon atom would be resistant to reduction. Initially, we synthesized TBDMS sulfide 32 from readily available 2-mercaptobenzoic acid 27 by modifying the route of Kasmai and Mischke for the preparation of 2-mercaptobenzaldehyde (Scheme ).…”