A New Synthesis of 1beta-Alkylcarbapenems Utilizing Eschenmoser Sulfide Contraction of the Novel Thiazinone Intermediates.
Novel syntheses of the 1beta-alkylcarbapenems were achieved on the basis of Eschenmoser sulfide contraction via the new bicyclic 1,3-thiazinone intermediates. 1,3-Thiazinones 7, 16, and 25 were effectively prepared from thioesters 5 and 22 using a C4-S bond formation process. The sulfide contraction reactions were performed by treatment of 7, 16, and 25 with base (NaH or KO-t-Bu) in the presence of triphenylphosphine to generate the corresponding carbapenem enolate 12, 17, and 26, which were trapped by (PhO)(2)POCl followed by the reaction with mercaptans to afford carbapenems 10a, 10b, 19, and 28, respectively.
Sakurai
Osamu
O
Lead Generation Research Laboratory, Lead Optimization Research Laboratory, Pharmaceutical Development Research Laboratory, and Research and Development Planning Division, Tanabe Seiyaku Co., Ltd., 3-16-89, Kashima, Yodogawa, Osaka 532, Japan.
Ogiku
Tsuyoshi
T
Takahashi
Masami
M
Hayashi
Masahito
M
Yamanaka
Takeshi
T
Horikawa
Hiroshi
H
Iwasaki
Tameo
T