Ginkgolides synthesis

Specific enolates by conjugate (Michael) addition An intermediate in Corey s ginkgolide synthesis A synthesis of jasmine ketolactone Tables of Enol Equivalents and Specific Enolates Modern Use of Specific Enolate Equivalents... 

A few examples should make modem approaches plain. In Corey s ginkgolide synthesis he needed the intermediate 117 and decided to make it by coupling two vinyl derivatives (see chapters 11 and 20), the one derived from a triple bond 118 and the other an enol derivative of a cyclic ketone 119. 

A key intermediate, 163, which possesses all but one chiral center of (+ )-brefeldin, has been prepared by the enantiocontrolled cycloaddition of the chiral fi,/3-unsaturated ester 162 to 154[107], Synthesis of phyllocladane skeleton 165 has been carried out by the Pd-catalyzed cycloaddition of the unsaturated diester 164 and cobalt-catalyzed cycloaddition of alkynes as key reactions[108]. Intramolecular cycloaddition to the vinylsulfone in 166 proceeds smoothly to give a mixture of the trans and cis isomers in a ratio of 2.4 1[109], Diastereocontrolled cycloaddition of the hindered vinylsulfone 167 affords a single stereoisomeric adduct, 168, which is used for the synthesis of the spirocarbocyclic ring of ginkgolide[l 10],... 

Diels-AIder reactions, I, 618 reactions, 1, 617-620 synthesis, 1, 614-616 2-Germoxetanes heterosubstituted germacyclobutanes and, 1, 596 Gewald synthesis thiophenes, 4, 888-889 ( )-Gingerol synthesis, 1, 453 (+)-(S)-Gingerol synthesis, I, 435 Ginkgolide A... 

The multistrategic retrosynthetic analysis of ginkgolide B, which led to the synthesis outlined below, is presented in Section 6.7 of Part One. The synthetic route, an enantioselective version of which was demonstrated, also led to ginkgolide A. 

An efficient enantioselective route for the total synthesis of ginkgolide B has been established by synthesizing the key intermediate A in an enantiomerically pure form (Ref. 2),... 

Based on the successful total synthesis of ginkgolide B, ginkgolide A was made by two different routes. 

Despite the structural relationship between ginkgolide B and bilobalide, retrosynthetic analysis of the latter produced a totally different collection of sequences. A successful synthesis of bilobalide was implemented using a plan which depended on stereochemical and FG-based strategies. A process for enantioselective synthesis was based on an initial enantioselective Diels-Alder step in combination with a novel annulation method. 

Of the many interesting and productive stages in Corey s synthesis of ginkgolide B, it is the intramolecular ketene-olefin [2+2] cycloaddition step that is perhaps the most impressive (see 14—>13). The conversion of 14 to 13 is attended by the formation... 

Corey s solution to the intimidating structural and stereochemical complexities of ginkgolide B features an impressive collection of powerful bond-forming strategies. The first total synthesis of ginkgolide B by the Corey group is a major achievement of contemporary organic synthesis. 

In addition to the [4+2] cycloaddition, intramolecular [2+2] photocycloaddition was also successfully used as a main procedure in the synthesis of (i)-ginkgolide B <00JA8453>. The studies on the model reactions and molecular mechanics calculation show that the stereochemistry of the substituents at C6 and C8 should influence severely the reaction diastereoselectivity. When syn-diastereomer 41 is subjected to irradiation the reaction gives a single diastereomer 42 in a quantitative yield since two substituents at C6 and C8 would be in pseudo-equatorial orientation in the chair-like transition state. 

While Ginkgo biloba achieves total biosynthesis of ginkgolides with great ease, it is only recently that chemical synthesis of these compounds has been accomplished. Initially, only the synthesis of hexahydro-5/f-dicyclopen-ta[6,clfuran-5a(6//)-ol, which represents the main framework of ginkgolides (rings A,B,D), was achieved [185]. Recently, however, using a sophisticated... 

Amri H, Drieu K, Papadopoulos V. (1997). Ex vivo regulation of adrenal cortical cell steroid and protein synthesis, in response to adrenocorticotropic hormone stimulation, by the Ginkgo biloba extract EGb 761 and isolated ginkgolide B. Endocrinology. 138(12) 5415-26. 

Amri H, Ogwuegbu SO, Boujrad N, Drieu K, Papadopoulos V. (1996). In vivo regulation of peripheral-type benzodiazepine receptor and glucocorticoid synthesis by Ginkgo biloba extract EGb 761 and isolated ginkgolides. Endocrinology. 137(12) 5707-18. 

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