Diolides synthesis

As indicated in the section describing the structures of natural dilactones, wentilactone B was wrongly assigned when the structure of 30-hydroxy-13,14,15,16-tetranorlabda-7,9(ll)-dien-(19,6(J),(12,17)-diolide was isolated. Our synthesis of this compound allows the reassignment of the structure of wentilactone B. Thus, the hydroxyl group of this natural podolactone should be relocated at C-2 with an a- configuration [87]. Two double cyclization steps were employed in this synthesis. The first involves the construction of the bicyclic skeleton via a Mn(III)-mediated... 

The first totai synthesis of the ichthyotoxic marine naturai product (-)-apiyoiide A was accomplished by Y. Stenstrom and co-workers. The compound has a 16-membered lactone ring, four (Z)-double bonds, as well as a stereogenic center. Numerous macroiactonization protocols were tested, but most of them gave the diolide (dimer) except for the Corey-Nicoiaou procedure. 

The first synthesis of vermiculine by Corey, outlined in Scheme 4.14, employed an isopropenyl group as a protected version of the acetone sidechain. Aldehyde 57, the Dibal reduction product of readily available dimethyl 2,2-dimethoxyglutarate, was condensed with dimethallyl cadmium and the resulting alcohol silylated to produce 58 (70%). Reduction of ester 58 to the aldehyde followed by two-carbon homologation afforded a 94% yield of a,P unsaturated ester 59. Hydrolysis of 59 to the to the acid and conversion to the 2-thiopyridyl ester (77%) set the stage for double lactonization. This transformation was accomplished by thermolysis of a diluted solution of the thioester, affording a 30% yield of the diasteromeric diolides 60a and 60b (1 1). The former was then converted by oxidation into the synthetic 56 and the latter into the meso isomer 61, both in 70% yield. 

Swinholide A is an interesting physiologically highly active marine metabolite with a macrocyclic diolide structure and a polyketide carbon skeleton. Recently the first total synthesis of 161 was reported by I. Paterson et al. (21). We focused on the synthesis of the tetrahydropyran part of the molecule as represented by compound 162. The particular feature of this ring is that it bears the largest substituent (at C-27) in an axial arrangement, as shown by the X-ray crystal structure of 161. 

The Seebach aglycone synthesis is also independently based on the aldol coupling of the dialdehydic diolide 282 and the ethyl ketone 288, which are prepared by the use of chiral building blocks, Roche ester 285 or diethyl (S)-malate (286) and ethyl (R)-3-hydroxybutyrate (287). 

Other groups have also used the Yamaguchi lactonization procedure to synthesize natural products, most notably Seebach in the synthesis of (+)-myscovirescine M2, a 27-membered lactone, in which the seco acid was converted to the lactone in 83% yield. Symmetrical diolides (8) have been prepared from unprotected seco acids in fair yields (eq 4) when other lactonization procedures failed. Unsymmetrical diolides require protected seco acids. ... 

---