Adam Golebiowski

High-pressure (4+2)cycloaddition of 1-methoxy-3-trialkylsilyloxybuta-1,3-dienes to butyl glyoxylate. Isolation of primary cycloadducts

Abstract High-pressure reactions of 1-methoxy-3-trialkylsilyloxybuta-1,3-dienes ( 1 , 2 ) with butyl glyoxylate ( 3 ) and isolation of the primary cycloadduct 5 as well as its simple chemical transformations are described.

Stereoselective addition of furyllithium to variously N,N-diprotected D-alaninals

Abstract A highly stereoselective route to derivatives of 2-amino-1-(2′-furyl)propan-1-ol via addition of furyllithium to variously N,N-diprotected d -alaninals is described. An efficient conversion of these compounds into aminosusar precursors - chiral uloses is also presented.

High-pressure (4+2)cycloaddition of 1-methoxybuta-1,3-diene to α-amino aldehydes. Influence of n-protecting groups on asymmetric induction

Abstract The stereochemistry of the high-pressure (4+2)cycloaddition reaction of 1-methoxybuta-1,3-diene with N -benzyloxycarbonyl-, N -phthaloyl-, and N -benzyl- N -tert-butoxycarbonyl- D -alaninal is discussed, and methyl 2,6-di- N -acetyl-α- D -purpurosaminide B is synthesized.

High-pressure [4+2] cycloaddition of 1-methoxy-1,3-butadiene to N,O-protected D-threoninals and D-allo-threoninals☆

Abstract High-pressure [4+2]cycloadditions of trans-1-methoxy-1,3-butadiene (3) to N,O-protected D -allo-threoninals (4) and D -threoninals (8) were studied. In all cases, 5,6-syn-adducts were the major products. The results are explained by α-chelation with Eu(fod)3 or by intramolecular hydrogen bonding.

Total synthesis of D,L-purpurosamine C

Abstract Methyl 2,6-diacetamido-2,3,4,6-tetradeoxy-α-D,L-erythrohexopyraaoside (methyl 2,6-N,N-diacetyl-D,L-purpurosaminide C) was synthesized from N-tert-butoxycarbonylaminoethanol and 1-methoxybuta-1,3-diene in a seven-step reaction sequence. (4+2)Cycloaddition of diene 1 to N-protected α-amino aldehyde 2 and hydroboration of the adduct formed are key steps in the synthetic sequence.

2-Substituted-2-amino-6-boronohexanoic acids as arginase inhibitors.

Substitution at the alpha center of the known human arginase inhibitor 2-amino-6-boronohexanoic acid (ABH) is acceptable in the active site pockets of both human arginase I and arginase II. In particular, substituents with a tertiary amine linked via a two carbon chain show improved inhibitory potency for both enzyme isoforms. This potency improvement can be rationalized by X-ray crystallography, which shows a water-mediated contact between the basic nitrogen and the carboxylic acid side chain of Asp200, which is situated at the mouth of the active site pocket of arginase II (Asp181 in arginase I). We believe that this is the first literature report of compounds with improved arginase inhibitory activity, relative to ABH, and represents a promising starting point for further optimization of in vitro potency and the identification of better tool molecules for in vivo investigations of the potential pathophysiological roles of arginases.

The cyclocondensation reaction of 1-benzoyloxy-2-tert-butyl-dimethylsilyloxy-4-methoxy-1,3-butadiene with N,O-protected D-threoninals and D-allo-threoninals

Abstract The zinc bromide-catalyzed reaction of 1-benzoyloxy-2- tert -butyldimethylsilyloxy-4-methoxy-1,3-butadiene ( 3 ) with N -carbobenzoxy- O -protected- D - allo - ( 4 ) and - D -threoninal ( 9 ) was studied. Pyrones 7a and 12a were transformed into diastereoisomers of lincosamine ( 16 and 19 ).

Synthesis of quaternary α-amino acid-based arginase inhibitors via the Ugi reaction

The Ugi reaction has been successfully applied to the synthesis of novel arginase inhibitors. In an effort to decrease conformational flexibility of the previously reported series of 2-amino-6-boronohexanoic acid (ABH) analogs 1, we designed and synthesized a series of compounds, 2, in which a piperidine ring is linked directly to a quaternary amino acid center. Further improvement of in vitro activity was achieved by adding two carbon bridge in the piperidine ring, that is, tropane analogs 11. These improvements in activity are rationalized by X-ray crystallography analysis, which show that the tropane ring nitrogen atom moves into direct contact with Asp202 (arginase II numbering). The synthetic routes described here enabled the design of novel arginase inhibitors with improved potency and markedly different physico-chemical properties compared to ABH. Compound 11c represents the most in vitro active arginase inhibitor reported to date.

Total synthesis of (+)-galantinic acid

N,O-Protected L-serinal (5) afforded with diene 4, pyrone 3 as a single product which was transformed into (+)-galantinic acid derivative 8.

High Pressure Organometallic Chemistry : Diastereoselectivity in Diels Alder Reactions of 2,3-Dimethyl-1,3-Butadiene with (Z)-3-Tributyl-Stannylacrylic Acid (-) Menthyl Ester

Abstract The effect of pressure (0.1 to 25OO MPa) on the asymmetric induction in the cycloaddition between (-)-menthyl 3-tributylstannyl-acrylate and 2,3-dimethyl-1,3-butadiene has been investigated under different solvent and temperature conditions. The high pressure considerably facilitates the addition but leads to a decrease or even an inversion of the diastereomeric excess. This behavior can be explained by a favored cisoid conformation of the ethylenic ester under high pressure.