Concept of Counterattack Reagents: Intramolecular Counterattack Strategy in the Synthesis of Biologically Active Isopenams

Abstract

A novel strategy was developed for the synthesis of isopenams in high yields. The strategy involves use of the intramolecular counterattack process in the conversions of (AE)-5 3(AE)-11, (AE)-6 3(AE)-12, and (AE)-19 3(AE)-11. Catalytic hydrogenation of (AE)-11 afforded isopenam (AE)-13, which possessed notable antimicrobial activities. Oxidation of (AE)-13 with KMnO 4 gave sulfone (AE)-15, which functioned as a potent inhibitor of various bacterial blactamases. Sulfone (AE)-15 exerted a great synergistic effect on antimicrobial agent (AE)-13. Results from the CVFF calculations of the C-2 b-epimer of isopenam 13 (i.e., 23) and the corresponding sulfone derivative 24 indicate the existence of a severe electronic repulsion between the b-lactam carbonyl and the C-2 carboxyl groups. Steric interaction also exists between the C-6 amide side chain and the C-2 carboxylic acid moiety in 23 and 24. These interactions, however, do not exist in the corresponding a-epimers 13 and 15.

Dimethyl 3,4,5,5-tetraphenyl-1,3-thiazolidine-2,2-dicarboxylate and 3,3-dichloro-2,2,4,4,3′-pentamethyl-r-2′,t-4′-diphenylcyclobutane-1-spiro-5′-1,3-thiazolidine

“…-diphenylcyclobutane-1-spiro-5 (Hwu et al, 1999;Pellegrini et al, 1999) and have also been explored as valuable starting materials for the preparation of more complex structures (Bringmann et al, 2000;Jin & Kim, 2002). The title compounds, (V) and (IX), were obtained by the [3+2]-dipolar cycloaddition of an azomethine ylide, generated in situ by thermal ring-opening of the appropriate aziridine in the presence of thiobenzophenone, (IV), or 3,3-dichloro-2,2,4,4-tetramethylcyclobutanethione, (VIII) (see scheme), according to the general protocol of Mloston  & Skrzypek (1990).…”

1,3-Thiazolidine derivatives from regioselective [2+3]-cycloadditions of azomethine ylides with thioketones

“…1,3-Thiazolidines may be used in the synthesis of pharmaceuticals such as immunomodulating drugs or antibiotics (Hwu et al, 1999;Pellegrini et al, 1999). Thioketones are recognized as`superdipolarophilic' compounds and combine smoothly with 1,3-dipoles to yield sulfur-containing ®vemembered heterocycles (Huisgen et al, 1995).…”

Solid solution of two diastereomers of [3a(R,S),7a(R,S)]-3-[(1′R)-1-phenylethyl]perhydro-1,3-benzothiazol-2-iminium chloride

“…A wide interest in thiazolidin-2-imines and related heterocycles is due to their pharmacological and biological activity such as local anesthetic, anti-seizure, anti-tubercular, anti-bacterial, anti-amoebic, anti-diabetic, anti-inflammatory, anti-oxidant and anti-fungal activity (Chaurasia, 1971;Eswaramoorthy et al, 1991;Zimenkovsky et al, 1999;Shankaran et al, 2004;Heinelt et al, 2004). Substituted 1,3-thiazolidines have also been explored as valuable starting materials for the preparation of more complex structures (Zask et al, 1990;Hwu et al, 1999;Jin & Kim, 2002). The most popular method to synthesize thiazolidines is the cyclization reaction of aziridines with heterocumulenes, such as phenyl isothiocyanate, in the presence of a catalyst [NaI; Campbell & Craig, 1980;Nadir & Basu, 1995; compounds of palladium(II); Baeg et al, 1995;Butter et al, 2000; or Bu 3 P; Wu et al, 2008].…”