H. M. R. Hoffmann

Asymmetric synthesis of the C(10)C(16) segment of the bryostatins

Abstract The C(10)ue5f8C(16) segment of the bryostatins has been synthesized (12 steps, 15 % overall yield) and a cyanohydrin based strategy was developed for coupling with a C(1)ue5f8C(9) model.

Asymmetric synthesis of the C(18)C(24) unit of lasonolide A

Abstract The C(18)ue5f8C(24) segment of lasonolide A has been prepared with complete chemodifferentiation of functionality.

Samarium diiodide-mediated pinacolization of 1,4-diketones —I. Stereoselective synthesis of fused mono-, bi- and tricyclic cyclobutane-1,2-diols

Abstract The title reaction has been applied to the synthesis of a variety of cis-cyclobutane-1,2-diols in good yield.

Synthesis of the C1C9 segment of bryostatin

Abstract The C1ue5f8C9 segment of bryostatin has been prepared in 11 steps in 21% overall yield.

Lipase mediated desymmetrization of meso-2,6-di(acetoxymethyl)-tetrahydropyran-4-one derivatives. An innovative route to enantiopure 2,4,6-trifunctionalized C-glycosides

Abstract The desymmetrization of several meso -configurated 2,4,6-trifunctionalized tetrahydropyrans was studied. Amongst the derivatives investigated the conformationally more rigid spiro ketal 8b afforded hydroxy-acetate (−)- 12 in excellent chemical yield and enantiomeric excess. The absolute configuration of the resulting 2,4,6-trifunctionalized C-glycosides was established by X-ray crystal diffraction.

DIASTEREOSELECTIVE SYNTHESIS OF FUNCTIONALIZED 9-RING ETHERS (OXONINS)

In response to the challenge of preparing medium ring ethers of the Laurencia class, a simple synthesis of functionalized, acyclic α,α′-chiral disecondary ethers has been developed. Stereocontrolled cyclization to 9-membered rings was effected in overall high yield by Pd(0) catalyzed allylic alkylation.

Synthesis of enantiopure C-glycosides and pseudo C-glycosides: Lewis-acid mediated heterolysis of methyl acetals

Lewis-acid mediated heterolysis of substituted methoxy acetals derived from anomeric [3.3.1] oxabicyclic lactones leads to enantiopure deoxy C-glycosides in excellent chemical yield. An alternative route to C-glycosidic esters involves simple one-step opening of [3.3.1] oxabicyclic lactones with in situ esterification.

Synthesis of 10,11-didehydro- and 10,11-dihydro-Quincorine and of the Quincoridine analogs: functionalized and enantiopure 1-azabicyclo[2.2.2]-octanes with four stereogenic centers

Abstract The convenient synthesis of 10,11-didehydro-QCI (2) and of 10,11-didehydro-QCD (4) as well as 10,11-dihydro-QCI (5) and 10,11-dihydro-QCD (6) is described. Conversion of the olefinic double bond of Quincorine® 1 and Quincoridine® 3 into the corresponding alkynes 2 and 4 involves twofold dehydrobromination, and an important application of the solid KOH/aliquat 336 system in the key step. The structure of didehydro-QCI (2) has been elucidated by X-ray crystal diffraction. The new alkynes 2 and 4 are more polar and more basic than QCI and QCD, respectively.

Polyannulated glycopyranosides via radical-mediated tandem reactions. Stereoselective synthesis of 6·5·6 dioxatricycles via 5-exo-trig, 6-endo-dig mode — III

Abstract A series of C-silylated enynols, e.g. 6-methyl-l-trimethylsilyl-hept-5-en-l-yn-4-ol (rac-A) was prepared and submitted to N-iodosuccinimide mediated iodoalkoxylation of tri-O-acetylglycal Thanks to the presence of the silyl group the resulting diastereomeric glycosides (S) A 1 and (R) A 1 were readily separated. Triethylborane/oxygen/ethyl iodide promoted iodine transfer afforded doubly annulated glycosides in a 5-exo-trigonal, 6-endo-digonal cascade. The required re-protection of the three acetoxy groups was carried out orthogonally. The newly installed iodocyclohexene moiety served as site for further functionalization, which was accomplished by metal-halogen exchange followed by electrophilic capture or by reduction/epoxidation.

ACYLATION AND O-SULFONYLATION OF QUINCORINE AND QUINCORIDINE. EFFICIENT INTRAMOLECULAR CATALYSIS

Abstract A convenient preparation of enantiopure O-acyl and O-sulfonyl derivatives of Quincorine® and Quincoridine® is described.