Synthesis, structure determination, and biological evaluation of destruxin E.
The total synthesis of destruxin E (1) has been achieved for the first time, and the stereochemistry of its chiral center at the epoxide has been determined to be (S). The cyclization precursor 3a was synthesized by solid-phase peptide synthesis. Macrolactonization of 3a utilizing MNBA-DMAPO, followed by formation of the epoxide, then furnished destruxin E. Its diastereomer, epi-destruxin E (2), was also synthesized in the same manner. Furthermore, the biological evaluation indicated that destruxin E exhibits V-ATPase inhibitory activity 10-fold greater than that of epi-destruxin E.
Yoshida
Masahito
M
Graduate School of Pharmaceutical Sciences, Tohoku University, 6-3 Aza-Aoba, Aramaki, Aoba-ku, Sendai 980-8578, Japan.
Takeuchi
Hisayuki
H
Ishida
Yoshitaka
Y
Yashiroda
Yoko
Y
Yoshida
Minoru
M
Takagi
Motoki
M
Shin-ya
Kazuo
K
Doi
Takayuki
T
D003500:Cyclization; D047630:Depsipeptides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D005656:Fungal Proteins / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D015394:Molecular Structure; D013237:Stereoisomerism; D025262:Vacuolar Proton-Translocating ATPases / Q000037:antagonists & inhibitors*
D047630:Depsipeptides; D005656:Fungal Proteins; D025262:Vacuolar Proton-Translocating ATPases; C040425:destruxin E