Tapas Paul

Concise Total Syntheses of (±)-Strychnine and (±)-Akuammicine†

Concise total syntheses of Strychnos alkaloids strychnine (1) and akuammicine (2) have been realized in 13 and 6 operations, respectively. Key steps include (1) the vinylogous Mannich reaction; (2) a novel, sequential one-pot spirocyclization/intramolecular aza-Baylis-Hillman reaction; and (3) a Heck cyclization. The synthesis of 1 proceeds via the Wieland-Gumlich aldehyde (26).

Total synthesis of (-)-4,8,10-tridesmethyl telithromycin.

Novel sources of antibiotics are required to address the serious problem of antibiotic resistance. Telithromycin (2) is a third-generation macrolide antibiotic prepared from erythromycin (1) and used clinically since 2004. Herein we report the details of our efforts that ultimately led to the total synthesis of (-)-4,8,10-tridesmethyl telithromycin (3) wherein methyl groups have been replaced with hydrogens. The synthesis of desmethyl macrolides has emerged as a novel strategy for preparing bioactive antibiotics.

Concise Total Synthesis of (+)-Crocacin C

The cytotoxic natural product (+)-crocacin C ( 1) has been synthesized in 10 linear steps from commercially available Evans chiral propionimide in 5% overall yield (8 steps from Evans chiral dipropionate synthon). No protecting groups were utilized.

Total synthesis of (+)-crocacin C.

Two approaches toward the total synthesis of cytotoxic polyketide natural product (+)-crocacin C (1) are described. The first approach, which was ultimately unsuccessful, was replaced altogether with a second that afforded target 1 in 10 linear steps from commercially available Evans chiral propionimide (5% overall yield). No protecting groups were utilized in the total synthesis of 1.