Hans Bieräugel

The first synthesis of the ABCD ring system of manzamine A. Construction of the macrocyclic ring D.

The synthesis of the ABCD ring system of manzamine A has been achieved using the olefin metathesis cyclization reaction for the crucial macrocyclic ring D formation step.

SYNTHESIS MEDIATED BY RING-CLOSING METATHESIS : APPLICATIONS IN THE SYNTHESIS OF AZASUGARS AND ALKALOIDS

The application of the ring-closing metathesis (RCM) reaction to the construction of a wide variety of nitrogen-containing ring systems is described. The examples include pyrrolizidine, indolizidine, and quinolizidine derivatives related to azasugars. A formal total synthesis of castanospermine (5) is presented. The utilisation of two RCM steps in the synthetic sequence leading to the multicyclic ABCDE nucleus 7 of the complex alkaloid manzamine A (6) is discussed.

Models of folate coenzymes. VII: Synthesis and carbon transfer reactions of N5,N10-methenyl and N5,N10-methylenetetrahydrofolate models

Abstract Carboxylate esters react with 1,2-diaminoethanes to yield imidazolines, which upon consecutive reaction with acetic anhydride or tosyl chloride and methyl iodide give imidazolinium salts that serve as models of N5,N10-(CH+)-tetrahydrofolate (THF) coenzymes (7a, b and 18a, b). Reduction of the latter salts with sodium borohydride or reaction with anions (R−) give the corresponding 5,10-[CH(H,R)]-THF models. Mono- and bifunctional nucleophiles react with 18a, b to yield carbon-transfer products 6-Alkylamino-1,3-dimethyluracils react with 1 tosyl-3,4,4-trimethylimidazolidine (the reduction product of 18b), in the presence of acetic acid, to form carbon transfer products via a mechanism which bears close analogy to the mechanism of action of thymidylate synthetase.

Models of folate coenzymes—VIII : An approach to yohimbane alkaloids via carbon-fragment transfer from N5, N10-methylenetetrahydrofolate models

Abstract 2-Substituted 1-tosyl-3,4,4-trimethylimidazolidines prepared by the addition of anions to 1-tosyl-3,4,4-trimethyl-2-imidazolinium iodide 1, react with tryptamine in the presence of acetic acid to give 1-substituted β-carboline derivatives. The salt 1 reacts with anions of 2-[2-(1,3-dithianyl)]benzoates 4a-c to give the corresponding imidazolidines 5a, 5b and 5c, respectively. These transfer the substituted fragment to tryptamine to give pentacyclic products corresponding to the yohimbane skeleton. The product from 5c yields, after reduction of both the amide and the dithiane function, the precursor of epi- and allo-yohimbanes.

Synthetic studies on manzamine A

The total synthesis of the ABCDE ring system of manzamine A, with the correct absolute stereochemistry at the chiral centers, is described. Key steps in the synthetic route are the formation of both the eight- and the thirteen-membered rings by an olefin metathesis cyclization reaction. The sponge alkaloid manzamine A (1) is a challenging synthetic target in view of its antileukemic and antibacterial activities and particularly due to its unique structure. It consists of a novel pentacyclic heterocyclic nucleus onto which a P-carboline ring system is attached as a pendant substituent. In this communication we wish to present a total synthesis of the chiral ABCDE ring system of the alkaloid (2) bearing a suitable substituent for elaboration of the P-carboline heterocycle, for the final stages of the synthesis.

An approach to vindoline skeleton utilizing substituted methylenetetrahydrofolate (5,10-CHR-THF) models

Abstract Starting from a substituted methylenetetrahydrofolate model [4-(2-N(1)-tosyl-N(3)-methyl-4,4-dimethylimidazolidyl)-3-ketobutanoate], an efficient synthesis of the pentacyclic system corresponding to vindoline is described.

Transfer of functionalized carbon fragments via substituted 5, 10-methylentetetrahydrofolate models. : Approach to dihydroindole and indole alkaloids.

Abstract 4-(2-N(1)-tosyl-N(3)-methyl-4-,4-dimethylimidazolidyl)-3-ketobutanoate reacts with tryptamine, in the presence of acetic acid, to give primary “carbon transfer” products, which can be conveniently converted to synthetically useful indole and dihydroindole derivatives.

Studies on the total synthesis of manzamine A

Progress towards the synthesis of the marine alkaloid manzamine A is described. The synthesis of the ABCD ring system has been achieved, with the macrocyclic D ring being formed by an olefin metathesis cyclization. Additionally, a chiral ABC tricyclic intermediate has been converted into the ring D-nor manzamine A skeleton.

Models of folate coenzymes-IX : Synthesis of d,l-pyridindolol

Abstract Reaction of the acetonide of 1-acetyl 3,4,4 - trimethyl 2 - [ 1,2 - dihydroxyethyl] imidazolidine - a substituted N5,N10 - methylenetetrahydrofolate model - with d,l-tryptophan hydrochloride, in the presence of acetic acid, leads to the formation of the known β-carboline precursor of d,l-pyridindolol in one practical step.

Mild and regioselective nitration of 1-deazapurine nucleosides using TBAN/TFAA

Abstract To obtain selectively functionalized 1-deazapurine nucleosides, the nitrating mixture tetrabutylammonium nitrate/trifluoroacetic anhydride (TBAN/TFAA) has been studied. This mixture demonstrated several merits: the use of an easy to handle reagent, mild reaction conditions and high selectivity for nitration in the pyridine ring. Nitration occurred at the α or β-position with respect to the pyridine nitrogen atom, depending on the substituents in the ring. Electron withdrawing substituents in the pyridine ring showed a positive effect on this nitration.