Synthesis of tetrahydrolipstatin and tetrahydroesterastin, compounds with a .beta.-lactone moiety. Stereoselective hydrogenation of a .beta.-keto .delta.-lactone and conversion of the .delta.-lactone into a .beta.-lactone

The Total Synthesis of ( - )-Tetrahydrolipstatin

“…All spectral data for the synthetic (-)-(1) are identical to that reported previously. [5][6][7][8][9][10][11][12][13][14][15][16] Conclusion (-)-Tetrahydrolipstatin (1) was prepared in 12 steps and 11.3% yield from ester (11). Bromolactonization afforded of the desired β-lactone regioisomers in quantitative yield and careful choice of solvent and reaction time facilitated good control over the lactone ring stereochemistry (6 : 1 trans/cis ratio).…”

“…[3,4] There has been considerable interest in tetrahydrolipstatin due to the growing awareness of obesity-related illness and several syntheses have been reported. [5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20][21] In each case the construction of the strained trans-β-lactone of (1) emerges as an important synthetic challenge. The majority of previously reported syntheses [5][6][7][8][9][10][11][12][13][14][15][16] use Adams' conditions for formation of the β-lactone from a β-hydroxy carboxylic acid precursor.…”

Pharmaceuticals

“…[272][273][274] The reaction of the enantiomerically pure hydroxy-ester with 2-bromooctanoyl chloride leads after an in-tramolecular Reformatzky reaction to the δ-lactone. Another approach involves the Ivanov reaction of the benzyl-protected hydroxy-aldehyde with octanoic acid.…”

Synthesis of α,β‐Unsaturated δ‐Lactones by Vinyl Acetate Mediated Asymmetric Cross‐Aldol Reaction of Acetaldehyde: Mechanistic Insights

“…We also successfully extended our methodology to the asymmetric synthesis of α,β‐unsaturated δ‐lactones, a motif that is a characteristic underlying element of many antiproliferative agents, immunosuppressants and inhibitors of different enzymes 19. In addition, α,β‐unsaturated δ‐lactones are a part of a wide variety of natural scaffolds, for example, fostriecin, callystatin, ( R )‐goniothalamin, asperlin, leptomycin B and kazusamycin A,20 or serve as intermediates in the synthesis of bioactive molecules, such as tetrahydrolipstatin21 and clavulactone 22. Owing to their importance, many methods have been developed for their synthesis, such as the hetero‐Diels–Alder (HDA) reactions of the Brassard diene with aldehydes or ketones,23–26 solid‐phase Diels–Alder cycloaddition,27 the annulation of open‐chain precursors,28 N‐heterocyclic‐carbene‐catalysed reactions of α‐bromo α,β‐unsaturated aldehydes,29 reactions of homoallylic alcohols with the lithium enolate of methyl acetate30 and enzymatic cyclisation31 (Figure 1).…”