Isolation, structural assignment, and total synthesis of barmumycin

Barmumycin was isolated from an extract of the marine actinomycete Streptomyces sp. BOSC-022A and found to be cytotoxic against various human tumor cell lines. On the basis of preliminary one- and two-dimensional (1)H and (13)C NMR spectra, the natural compound was initially assigned the structure of macrolactone-type compound 1, which was later prepared by two different routes. However, major spectroscopic differences between isolated barmumycin and 1 led to revision of the proposed structure as E-16. On the basis of the synthesis of this new compound, and subsequent spectroscopic comparison of it to an authentic sample of barmumycin, the structure of the natural compound was indeed confirmed as that of E-16.     

The first total synthesis of xenitorins B and C: assignment of absolute configuration

Starting from (-)-beta-pinene, the first total synthesis of xenitorins B and C has been accomplished, which also allowed the assignment of their absolute configuration.     

Isoaurostatin: total synthesis and structural revision

Isoaurostatin, a topoisomerase I inhibitor isolated from Thermomonospora alba has been synthesized for the first time from 2,4-dihydroxyacetophenone via 6-methoxybenzo-2(3H)-furanone in five steps. The E-isomer was converted into Z-isomer, but spectroscopic data of either of these two isomers did not match with those of the natural product. The structure of isoaurostatin has been revised to a known isoflavone, daidzein (2), based on careful analysis of spectroscopic data.     

Azedaralide: total synthesis, relative and absolute stereochemical assignment

Azedaralide, a potentially advanced intermediate for the total synthesis of various tetranortriterpenes, was constructed utilising the Fernández-Mateos protocol and assigned both relative and absolute stereochemistries. Both asymmetric aldol and classical chiral resolution attempts failed to deliver pure enantiomers whereas preparative chiral chromatography resolved racemic azedaralide with ease.     

Lasonolide A: structural revision and total synthesis

The proposed structure of lasonolide A was synthesized employing radical cyclization reactions of beta-alkoxyacrylates for preparation of the tetrahydropyranyl units A and B, but the spectroscopic data did not match those of the natural product. Both enantiomers of a revised structure featuring 17E,25Z double bonds were synthesized, and the (-)-isomer was found to be the biologically active enantiomer.     

Feigrisolide C: structural revision and synthesis

[Carbohydrate structure: see text] The original macrodiolide structure proposed for feigrisolide C was incorrect. The true structure of feigrisolide C was identified as (2'S,3'S,6'R,8'R)-homononactoyl (2R,3R,6S,8S)-nonactic acid, which was confirmed by total synthesis.     

Gold catalysis: efficient synthesis and structural assignment of jungianol and epi-jungianol

Starting from 2-methylfuran and crotonaldehyde, both jungianol and epi-jungianol were prepared by a six-step sequence including a gold-catalyzed arene synthesis and a photochemical S(N)2-like reduction with lithium aluminum hydride. Not a single protective group was needed in the entire synthesis. With both diastereomers in hand, the stereochemical assignment in the literature could be corrected by means of a thorough (1)H NMR spectroscopic analysis and an X-ray diffraction study on an epi-jungianol derivative.     

Total synthesis and complete structural assignment of thiocillin I

The total synthesis of the thiopeptide antibiotic, thiocillin I, is described. This work unequivocally defines the full structure (constitution and configuration) of the natural product as 1.     

Lobatamide C: total synthesis,stereochemical assignment,preparation of simplified analogues,and V-ATPase inhibition studies

The total synthesis and stereochemical assignment of the potent antitumor macrolide lobatamide C, as well as synthesis of simplified lobatamide analogues, is reported. Cu(I)-mediated enamide formation methodology has been developed to prepare the highly unsaturated enamide side chain of the natural product and analogues. A key fragment coupling employs base-mediated esterification of a beta-hydroxy acid and a salicylate cyanomethyl ester. Three additional stereoisomers of lobatamide C have been prepared using related synthetic routes. The stereochemistry at C8, C11, and C15 of lobatamide C was assigned by comparison of stereoisomers and X-ray analysis of a crystalline derivative. Synthetic lobatamide C, stereoisomers, and simplified analogues have been evaluated for inhibition of bovine chromaffin granule membrane V-ATPase. The salicylate phenol, enamide NH, and ortho-substitution of the salicylate ester have been shown to be important for V-ATPase inhibitory activity.     

Total synthesis and structural elucidation of azaspiracid-1. Final assignment and total synthesis of the correct structure of azaspiracid-1

The molecular structure of azaspiracid-1, a neurotoxin isolated from mussels, has been elucidated by total synthesis which also enriched its supplies. The degradatively derived fragments of this marine biotoxin, compounds 5 (EFGHI), 6 (FGHI), and 40 (ABCD), were matched with synthetic materials, thus confirming their structural identities. Based on this detective work, a new structure of azaspiracid-1 (i.e., 1) was proposed and constructed by total synthesis. The final strategy for the total synthesis of azaspiracid-1 featured a dithiane anion (C(21)-C(27) fragment) reacting with a pentafluorophenol ester (C(1)-C(20) fragment) followed by a Stille-type union of an advanced allylic acetate substrate (C(1)-C(27) fragment) with a vinyl stannane as the main coupling processes to assemble the carbon skeleton of the molecule. In addition to the total synthesis of azaspiracid-1 (1), the syntheses of its C(1)-C(20) epimer (2) and of several truncated analogues for biological investigations are described.     

First total synthesis and assignment of the stereochemistry of crispatenine

The first racemic and enantioselective synthesis of crispatenine 1 has been achieved, which involved a few steps, enabling the assignment of the absolute and relative configurations.     

Total synthesis and absolute stereochemical assignment of kibdelone C

Kibdelones are hexacyclic tetrahydroxanthones and potent anticancer agents isolated from an Australian microbe. Herein, we describe the synthesis of a chiral, nonracemic iodocyclohexene carboxylate EF ring fragment of the kibdelones employing an intramolecular iodo halo-Michael aldol reaction and its merger with an ABCD ring fragment to afford the congener kibdelone C.     

Asymmetric total synthesis and structural elucidation of NFAT-68

Total synthesis of NFAT-68 (7) has been achieved and its relative stereochemistry has been determined. A key step thereof is the utilization of the chelation-controlled vinylogous Mukaiyama aldol reaction (VMAR) to stereoselectively synthesize the syn-aldol product 8. This developed chemistry is anticipated to have wider application in total syntheses of many other natural products.     

The first total synthesis and structural determination of benzopyrenomycin

The first total synthesis and structural determination of benzopyrenomycin has been achieved. This synthesis contains remarkable transformations including cyclization to afford the benzanthrone skeleton, syn-selective vinylogous Mukaiyama aldol reaction, and radical cyclization with the benzanthrone attaching the iodoalkane chain.     

The first total synthesis and structural determination of lagunamycin

Lagunamycin (1) has been synthesized by using our developed remote stereoinduction, Knorr condensation, periodinane oxidation, and diazonation. This enantioselective synthesis determined the absolute configuration of lagunamycin. Existence of rotational conformers was confirmed by NMR studies.     

The total synthesis and structural revision of stagonolide D

The total synthesis of the putative structure of stagonolide D has been completed. The relative and absolute configuration of stagonolide D was established by synthesizing its optical antipode. The adopted strategy involves the construction of the central macrolide employing ring-closing metathesis (RCM), followed by selective protecting group manipulations and a final concomitant -OTBS deprotection and displacement of an -OMs placed next to it, resulting in the formation of the epoxide ring.