Total synthesis of (+)-dihydrocompactin

Abstract

The total synthesis of (+)-dihydrocompactin 1 has been achieved by employing the double Michael reaction of 3-tert-butyldimethylsilyloxy-I -acetylcyclohexene with methyl crotonate as a key step.T All yields refer to pure isolated products, which exhibited satisfactory lH NMR, IR and mass spectral and/or elemental analyses.

Total synthesis of (+)-dihydrocompactin

“…Alternatively, the Shapiro reaction ' was tested to introduce the double bond at (2)(3)(4)(5)(6)(7)(8)(9)(10). As noted above, the 7).…”

“…Alternatively, the Shapiro reaction ' was tested to introduce the double bond at (2)(3)(4)(5)(6)(7)(8)(9)(10). As noted above, the 7). Selective protection of the primary alcohol of diol 29 as a pivalate 37 and then the secondary alcohol as a tertbutyldimethylsilyl ether (compound 38), followed by deprotection of the pivaloyl group with LAH afforded the alcohol 39 in 85% yield (overall in three steps).…”

“…[a]D -101. olefinic H) and 7.4 ( 5 H,br,ArH); m/z 456 (M', 0.7%), 354 (7), 188 (15), 121 (100) and 57 ( 18 -To a stirred solution of the crude diester 50 in methanol (2 cm3) was added a methanolic solution of potassium hydroxide (0.1 mol dm3 solution; 10 cm3, 1 mmol), and the resulting solution was stirred overnight at room temperature. The solution was poured into water and neutralised with dil.…”

A Chemoenzymatic Approach to Optically Active 5-Hydroxy-3-oxo-carboxylates

“…2 As well as other natural products, such as manoalide, 3 compaction and (+)-dihydrocompaction, 4 (-)-pestalotin, 5 bryostatin 6 etc. 5-Hydroxy-3-oxo-carboxylates can also react with an equivalent of aldehyde by a tandem Knoevenagel reaction in presence of BF 3 ·Et 2 O to synthesize single diastereomers of highly substituted tetrahydropyran-4-ones that are ubiquitous in natural product area.…”

“…Methods for the synthesis of optically active alcohols have been developed to give a variety of precursors of biologically active natural products, 1 among them optically active 5-hydroxy-3-oxo-carboxylates can be easily converted to 6-substituted-4-hydroxy lactones which are an important component of inhibitors of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase such as compactin and mevinolin. 2 As well as other natural products, such as manoalide, 3 compaction and (+)-dihydrocompaction, 4 (-)-pestalotin, 5 bryostatin 6 etc. 5-Hydroxy-3-oxo-carboxylates can also react with an equivalent of aldehyde by a tandem Knoevenagel reaction in presence of BF 3 •Et 2 O to synthesize single diastereomers of highly substituted tetrahydropyran-4-ones that are ubiquitous in natural product area.…”