Isovaleryl fluoride

Isovaleryl CoA is oxidized in a reaction similar to that found for other acyl CoA compounds to senecioyl CoA. This imsaturated thioester is a substrate for crotonase and is hydrated to j3-hydrosyisovaleryl CoA (HIV CoA). An unusual type of reaction converts this product to /3-hydroxy- 8-methyl glutaryl CoA (HMG CoA). Free CO2 is not fixed directly, but is first activated in a reaction with ATP. The activating enzyme H enzyme was purified as a hydroxylamine and bicarbonate dependent ATP-splitting enzyme the initial products are believed to be AMP-CO2 and pyrophosphate. This enzyme is different from a fluoride, bicarbonate dependent ATPase that has been shown to form... 

The synthetic technique is summarized in Scheme 3. Reaction of chaparrin (41b) with tert-butyldimethylsilyl chloride 11) afforded the crystalline disilyl derivative (93). The latter was obtained in better yield by silylation of (41b) with tert-butyldimethylsilyl enol ether of pentane-2,4-dione 105). The hydroxyl function at C-1 of (93) was effectively protected using trimethylsilyl triflate to afford the trisilyl lactone (94) which upon treatment with lithium diisopropylamide (LDA) and subsequent exposure to MoOs-pyridine-HMPA (M0O5PH) 104) gave the required 15-hydroxy lactone (95). Treatment of the latter with isovaleryl chloride afforded the crystalline ester (96) which was selectively desilylated to (97). Oxidation of the free allylic hydroxyl and complete desilylation of the resulting disilyl enone with tetrabutylammonium fluoride (BU4NF) afforded the natural cytotoxic quassinoid castelanone (34). 

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