Total synthesis of (+/-)-halichlorine, (+/-)-pinnaic acid, and (+/-)-tauropinnaic acid.

The related marine natural products halichlorine, pinnaic acid, and tauropinnaic acid have been synthesized. The described route provided access to all three compounds from a common, late-stage intermediate. The synthesis began with 1-pyrrolidino-1-cyclopentene from which an intermediate possessing the three contiguous stereocenters of the natural products was synthesized in just four steps.

Synthesis of tricolorin F.

A hetero-trisaccharide resin glycoside of jalapinolic acid known as tricolorin F has been synthesized. The approach involved the preparation of intermediate 5 and a subsequent coupling reaction with imidate 6 to produce disaccharide 7, which after deacetylation generated intermediate 8. A further coupling between this glycosyl acceptor and the quinovose glycosyl donor 9 resulted in the formation of the tricoloric acid C derivative 10.

Multigram synthesis of the C29-C51 subunit and completion of the total synthesis of altohyrtin C (spongistatin 2).

A multigram synthesis of the C29-C51 subunit of altohyrtin C (spongistatin 2) has been accomplished. Union of this intermediate with the C1-C28 fragment and further elaboration furnished the natural product. Completion of the C29-C51 subunit began with the aldol coupling of the boron enolate derived from methyl ketone 8 and aldehyde 9.

A second-generation synthesis of the C1-C28 portion of the altohyrtins (spongistatins).

A practical second-generation synthesis of an advanced intermediate in our total synthesis of altohyrtin C (spongistatin 2) has been developed. A new approach to the C1-C15 (AB) portion features a vinyllithium addition to an aldehyde followed by a palladium-catalyzed allylic reduction to install the troublesome C13-C15 segment. Our general approach to the C16-C28 (CD) spiroketal has been retained, but some improvements have been made.

The pyridoacridine family tree: a useful scheme for designing synthesis and predicting undiscovered natural products.

The pyridoacridine natural products represent a large and growing class and serve here to illustrate the wealth of information that can be extracted by comparing natural products on the basis of structure and occurrence.

Oxidative fragmentation of pregna-14,16-dien-20-ones to 14 beta-hydroxyandrost-15-en-17-ones.

Two methods have been developed for efficient conversion of pregna-14,16-dien-20-ones into 14 beta-hydroxyandrost-15-en-17-ones. One procedure consists of treatment of the ring-D dienone successively with sodium borohydride and singlet oxygen. The reaction is illustrated by the conversion of pregna-14,16-dien-20-one 1 into 14 beta-hydroxyandrost-15-en-17-one 3, via the corresponding allylic alcohol 2.

Regiochemistry in 1,3-dipolar cycloadditions of the azomethine ylide formed from diethyl aminomalonate and paraformaldehyde.

The azomethine ylide derived from the condensation of diethyl aminomalonate with paraformaldehyde undergoes 1,3-dipolar cycloadditions with acrylate and propiolate derivatives. Contrary to a previous report, these reactions yield mixtures of regioisomers generally favoring the 2,2,3-trisubstituted product. However, the relative quantity of the 2,2,4-trisubstituted product formed increases with an increase in the size of the activating group on the dipolaroplile.

Synthesis of the C1-C28 Portion of Spongistatin 1 (Altohyrtin A).

A synthetic approach was developed to the C1-C28 subunit of spongistatin 1 (altohyrtin A, 65). The key step was the coupling of the AB and CD spiroketal moieties via an anti-aldol reaction of aldehyde 62 and ethyl ketone 57. The development of a method for the construction of the AB spiroketal fragment is described and included the desymmetrization of C(2)-symmetric diketone 10 and the differentiation of the two primary alcohols of 16.

Total Synthesis of (+/-)-Cylindricines A and B.

Cylindricine A (1) and cylindricine B (2) have been synthesized in 11 steps and 19% overall yield. The key reaction involves the addition of an organocopper species to a bicyclic vinylogous amide, which provides complete stereocontrol over the installation of the hexyl side chain.

Total Synthesis of Myxalamide A.

The polyene antibiotic myxalamide A (1) has been prepared by total synthesis. The synthesis illustrates a useful strategy for synthesis in which the high 1,2-stereocontrol achievable with the aldol reaction can be parlayed by other stereoselective processes so as to give compounds having two or more stereocenters with remote relationships. Application of the Evans asymmetric aldol reaction to aldehyde 13 gives the beta-hydroxy imide 17.

A Biomimetic Approach to the Discorhabdin Alkaloids: Total Syntheses of Discorhabdins C and E and Dethiadiscorhabdin D.

The characteristic spirodienone structure of the discorhabdin alkaloids is readily formed by reaction of the tyramine-substituted indoloquinonimines 26, 35, and 36 with cupric chloride, triethylamine, and oxygen. This cyclization provides a possibly biomimetic route to discorhabdins C and E (41 and 42). The unbrominated spirodienone 40 reacts with hydrogen over Pd/C to give enone 46.

Total Synthesis of Tricolorin A.

Tricolorin A (1) is a novel tetrasaccharide macrolactone that is a natural herbicide. In this paper is reported a total synthesis of 1. Coupling of hydroxy ester 18 with D-fucosyl trichloroacetimidate 23 gave fucoside 24.

Total Syntheses of (-)-Papuamine and (-)-Haliclonadiamine.

The pentacyclic marine alkaloids (-)-papuamine (1) and (-)-haliclonadiamine (2) have been prepared by total synthesis. The synthesis began with (-)-8, which was converted into diester 20 by way of bis-mesylate 17, dinitrile 18, and diacid 19. Dieckmann cyclization of 20 provided keto ester 21, which was transformed into acetal 22.