Synthesis of both enantiomers of hiburipyranone

TETRAHEDRON Tetrahedron54 (I 998) X975-8984

Pergamon

Synthesisof Both Enantiomers of Hiburipyranone Kanako Uchida, Hidenori Watanabe and Takeshi Kitahara*

Received27 April 1998;accepted29 May 1998

Abstract: employing compound

Both enentiomersofhiburipyranone, acytotoxic metabolite o~marines~nge, ~~synt~sized Sharpless’ asymmetric ~h~~oxy~at~o~ as a key step and absolute con~~~mt~o~ of the natural at C-3 position was dete~in~ to be R.O 1998 EIsevier Science Ltd. All rights reserved. Keywords:

Asymmetric

Synthesis;

Cytotoxins;

Isocoumarins;

Hiburipyranone.

INTRODUCTION Hiburipyranone (1, Fig. 1) was isolated’ in 1991 by Fusetani et ul. from a marine sponge IV&C& C&KWVW It has a 3,4-~hydrois~oum~in skeleton and is cytotoxic against P38X murine leukemia cells (IC s0 = 0.19 pglml). Although racemic hiburipyranone was synthesized’ by us in 1997, absolute coufiguration at C-3 position has not been clarified. Herein, we report an enantioselective synthesis of (Q-1 and (S)-1 and determination of the absolute con~guration of natural hiburipyr~one as a part of our synthetic studies on is~oum~ins, which have rather simpie structureswith many remarkable bioactivities. OH 0

1 ~iburipyranone

Fig. 1

RESULTS AND DISCUSSION In our initial synthetic study, we adopted the same strategy with our acetophthalidin synthesis’ as shown in Scheme 1. Dihydroxylation of an olefin 3 gave a phthalide 4 directly under the usual AD reaction conditions.’ Deoxygenation at the benzylic position of the phthaiide 4 was examined in detail; (a) hydrogenolysis using Pd

~0~020~8/$19.00 0 1998 ElsevierScienceLtd. AH HI: 80040-4020(98)00511-O

rights

reserved.