Hyperolactones A (1) and C (3) have been synthesized starting from (S)-malic acid by a straightforward route. The unique spirolactone skeleton was efficiently constructed by one-pot reaction as a key step. The absolute stereochemistry of hyperolactones was unambiguously established by this synthesis. (2) and (-)-hyperolactone C (3), were also isolated from the same plant as minor components in 1995 [2]. The gross structure of 1 and its relative stereochemistry were determined by means of extensive spectroscopic studies and chemical transformation, and was finally confirmed by X-ray crystallographic analysis. These compounds possess a common spirolactone skeleton (anti-orientation at the stereogenic center C-5 in 2 as compared with 1 and 3), and some novel characteristics of the structure are (1) a highly substituted 1,7-dioxaspiro[4,4]non-2-ene-4,6-dione skeleton; (2) a strained 2,2,5-trisubstituted 3(2H)furanone ring system. Owing to their structural uniqueness, compound 1 and structurally related natural products are good targets for total synthesis [3]. We now describe herein the synthesis of 1 and 3 in a stereoselective fashion, which enables us to establish their absolute stereochemistry unambiguously. Synthesis of the Side Chain Units 8 and 14.The requisite aldehyde 8 was synthesized as shown in Scheme 1. The β-keto ester 6 was obtained by the Collins oxidation of the β-hydroxy ester 5, which was prepared from ethyl bromoacetate and benzaldehyde 4 by the Reformatsky reaction [4]. The keto ester 6 was heated with ethylene glycol containing a small amount of p-toluenesulfonic acid in benzene to give the ketal 7 in 73% yield. Diisobutylaluminium hydride reduction of 7 afforded the aldehyde 8 in 78% yield.

Butalactin (1a) and lactone II (2a) have been synthesized starting from (S)-malic acid and sorbic acid by a straightforward route. The absolute stereochemistry of 1a and 2a was unambiguously established by this synthesis.

All four possible stereoisomers of lactone II isolated from Streptomyces sp. Go 40/10, an autoregulator, have been efficiently synthesized in a stereoselective manner starting from (S)-malic acid and sorbic acid, and the absolute configuration was determined to be 2S, 3S, 9R, 10S.

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