Stereoselective Total Syntheses of Guanacastepenes N and O.

Total syntheses of (±)-guanacastepenes N and O were accomplished with 2-cycloheptenone as starting material. The six- and five-membered rings of the core [5, 7, 6] ring skeleton were constructed with an intramolecular Diels-Alder reaction and α-carbonyl radical cyclization. The quaternary centers and their stereochemistry were established with sequential Cu(I)-mediated conjugate additions.

Synthesis and antiproliferative activities of ottelione a analogues.

Through the syntheses of its C-1 desvinyl, C-7 methylene, C-7 exocyclic ethylidene, and various C-3 phenylmethyl analogues, the structure-activity relationship of antimitotic ottelione A (4) against tubulin and various cancer cells was established. The results indicated that compound 4 was a colchicine-competitive inhibitor and that the C-1 vinyl group is unnecessary for its potency, whereas the C-7 exocyclic double bond is essential, possibly because of its irreversible interaction with tubulin. Further optimization of the substituents on the phenylmethyl group at the C-3 position generated compound 10g with a 3'-fluoro-4'-methoxyphenylmethyl substituent, which was 6-38-fold more active against MCF-7, NCI-H460, and COLO205 cancer cells relative to 4.

Stereoselective total synthesis of (±)-peribysin E.

Radical cyclization of iodoketone 3 afforded cis-hydrindanone 8. Compound 8 was converted into key intermediate 5 via conventional transformations. Annulation of a spiro-lactal unit to 5 was pursued with three different approaches.

Enantioselective total synthesis of otteliones A and B.

Enantioselective total synthesis of otteliones A and B was accomplished. The key steps are radical cyclization of an alpha-iodoketone to construct the cis-hydrindanone skeleton and Suzuki-Miyaura coupling to incorporate the aromatic group. (+)-Ottelione A was converted to (-)-ottelione B on treatment with NaOH in THF.

Total syntheses of (+/-)-axamide-1 and (+/-)-axisonitrile-1 via 6-Exo-dig radical cyclization.

Total syntheses of (+/-)-axamide-1 (1) and (+/-)-axisonitrile-1 (2) were accomplished by using the alpha-carbonyl radical cyclization as the key step. Thienylcyanocuprate 24 mediated conjugated addition of 5-(trimethylsilyl)-4-pentynylmagnesium chloride (23) to 3-methylcyclopenten-1-one (22) and subsequent treatment with TMSCl afforded silyl enol ether 25. Iodination of 25 with NaI and m-CPBA afforded alpha-iodoketone 21.

An expedient route to Montanine-type Amaryllidaceae alkaloids: total syntheses of (-)-brunsvigine and (-)-manthine.

The first total syntheses of (-)-brunsvigine (1) and (-)-manthine (2) were accomplished in 10 and 18 steps, respectively. (-)-Quinic acid was converted to enone 12 in five steps. Iodination of enone 12 followed by stereoselective reduction yielded alpha-iodo allylic alcohol 16.

Intermolecular radical addition reactions of alpha-iodo cycloalkenones and a synthetic study of the formal synthesis of enantiopure fawcettimine.

The generation of alpha-carbonyl vinyl radicals from alpha-iodo cycloalkenones, the scope of their participation in intermolecular addition reactions with electron-withdrawing olefins are studied and a synthetic study of the formal synthesis of enantiopure fawcettimine using this reaction is described.

Enantiospecific total synthesis of (-)-bakkenolide III and formal total synthesis of (-)-bakkenolides B, C, H, L, V, and X.

A concise enantiospecific synthesis of (-)-bakkenolide III was accomplished from (S)-(+)-carvone. The key step involved radical cyclization of an iodoketone intermediate which afforded the cis-hydrindanone skeleton. Further synthetic transformations generated bakkenolide III, which also constitutes the formal total synthesis of (-)-bakkenolides, B, C, H, L, V, and X.

Photoinduced atom-transfer cyclization of alpha-iodocycloalkanones bearing an allenyl side chain.

[reaction: see text] Irradiation of alpha-iodocycloalkanones bearing an allenyl side chain with a sunlamp effected atom-transfer cyclization to give cyclized products in good yield. A mechanism, involving radical atom-transfer cyclization accompanied by 1,5- and 1,4-hydrogen transfers, is proposed.

Synthesis of a highly hindered hydrindanone via alpha-carbonyl radical cyclization: enantiospecific formal syntheses of (-)-pinguisenol and (-)-alpha-pinguisene.

An enantiospecific synthesis of Schinzer's ketone 3 from (R)-(+)-pulegone via alpha-carbonyl radical cyclization was accomplished. This work also constitutes an enantiospecific formal syntheses of (-)-pinguisenol and (-)-alpha-pinguisene. The intermediate ketone 4 would be useful for the synthesis of other pinguisane-type sesquiterpenes.

Anionic cyclization approach toward perhydrobenzofuranone: stereocontrolled synthesis of the hexahydrobenzofuran subunit of avermectin.

A facile anionic cyclization approach toward stereocontrolled synthesis of the hexahydrobenzofuran subunit 3 of avermectin is described. As a model study, treatment of iodo compound 7 with n-BuLi at -100 degrees C effected metal-halogen exchange and subsequent anionic cyclization to afford perhydrobenzofuranone 8. For the total synthesis of subunit 3, compound 9 was dihydroxylated to give diol 10.

alpha-Carbonyl Radical Cyclization Approach toward Angular Triquinanes: Total Synthesis of Enantiomerically Pure (-)-5-Oxosilphiperfol-6-ene.

An alpha-carbonyl radical cyclization approach toward synthesis of angular triquinanes is described. As a model study, conjugate addition of 4-(trimethylsilyl)-3-butynylmagnesium chloride to enone 7 followed by trapping of the enolate with chlorotrimethylsilane gave trimethysilyl enol ether 8. Iodination of 8 with a mixture of NaI and m-CPBA afforded iodo ketone 6.