0000000000376863
AUTHOR
Ari M. P. Koskinen
Model studies on a diastereoselective synthesis of the C(33)–C(37) fragment of Amphotericin B
Abstract A new, short and highly diastereoselective synthetic route aiming at the C(33)–C(37) fragment of Amphotericin B has been developed. Studies with a model aldehyde (benzaldehyde) have given very promising results: the desired stereochemistry of all four stereocenters of the target molecule has been achieved with high diastereoselection. The stereochemistry of three key intermediates and the target segment has been confirmed by X-ray crystallography.
Diastereoselective formation of highly functionalised α-substituted amino acid derivatives via aldol addition
Abstract Highly diastereoselective aldol additions of (2 R ,4 S )-3- tert -butyl 4-methyl 2- tert -butyloxazolidine-3,4-dicarboxylate ( 1 ) are reported. The utility of the highly substituted oxazolidines of type 1 for diastereoselective α-addition of the fully protected amino acid l -serine with achiral and chiral carbonyl compounds is demonstrated and the relative and absolute configuration of the aldol products are discussed on the basis of NOESY data and solid state structures of selected examples. The aldol products represent highly useful intermediates in the syntheses of sphingosine-related metabolites.
Novel γ-turn mimetics with a reinforced hydrogen bond
Abstract Pyridylmethylphenols 2 can mimic the geometry of γ-turns. Hydrogen bonding in 2 has been characterized by X-ray crystallography, IR and NMR spectroscopy, and molecular modeling.
Polyhydroxylated indolizidine alkaloids-synthesis of dideoxycastanospermine
The key transformation developed in this work is the anti-Kishi selective dihydroxylation, which proceeds by way of intramolecular participation of the nitrogen protecting group to furnish the desired stereochemistry required for castanospermine like structures. In this paper, we completed a first syn-thesis of a novel dideoxycastanospermine 6. Peer reviewed
The Reaction Mechanism of Spirocylization and Stereoselectivity Studies for the Calyculin C16 -C25 Fragment
The mechanism of the double intramolecular hetero-Michael addition, a key reaction in the planned synthesis of the natural product calyculin C, has been studied by NMR. The cyclization follows Baldwin’s rules and proceeds first through a six-membered ring closure (6-endo-dig), followed by a five-membered ring cyclization (5-exo-trig). (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2005)
Stereocontrolledα-Alkylation of Fully ProtectedL-Serine
Diastereoselective alkylation of the (2S,4S) and (2R,4S) diastereomers of 3-tert-butyl 4-methyl 2-tert-butyl-1,3-oxazolidine-3,4-dicarboxylate (1a/b) is reported. Formation of both diastereomers of these oxazolidines was achieved by changing the order of protection steps, and their relative and absolute configurations were determined by NOESY spectroscopy. The use of the bulky ring substituent tBu together with Boc as the N-protecting group led to the exclusive formation of only one alkylated diastereomer. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004)
An enantioselective synthesis of the C(33)–C(37) fragment of Amphotericin B
An enantioselective synthesis of the C(33)–C(37) tripropionate fragment of Amphotericin B has been developed in only 6 steps. Peer reviewed
A Simple Organocatalytic Enantioselective Synthesis of Pregabalin
This paper describes a new procedure for the enantioselective synthesis of the important anticonvulsant drug Pregabalin, which shows biological properties as the (S) enantiomer only. The key step of the synthetic sequence is the Michael addition reaction of Meldrum's acid to a nitroalkene mediated by a quinidine derived thiourea. A variety of novel catalysts bearing different groups at the thiourea moiety were synthesized and tested. The most successful catalyst that incorporates a trityl substituent provided up to 75 % ee of (S)-4. The conjugate addition reaction was carried out on a multigram scale with low loadings of catalyst (10 mol-%). Moreover, the catalyst can be recycled showing th…