Variable Strategy toward Carbasugars and Relatives. 4.¹ Viable Access to (4a-Carbapentofuranosyl)amines, (5a-Carbahexopyranosyl)amines, and Amino Acids Thereof

Abstract

A chiral, divergent synthesis of two carbafuranosylamines, 1 and 2, two carbapyranosylamines, 3 and 4, two carbafuranosylamino acids, 5 and 6, and two carbapyranosylamino acids, 7 and 8, has been achieved. Highlights of the procedure include the following: a diastereoselective crossed vinylogous Mukaiyama aldol coupling between N-(tert-butoxycarbonyl)-2-[(tert-butyldimethylsilyl)oxy]pyrrole (TBSOP, 9) and 2,3-O-isopropylidene-D-glyceraldehyde (10) for the assembly of the target compound carbon backbone; a high-yielding silylative cycloaldolization that gives the cyclopentanoid and cyclohexanoid motifs; and a reductive or hydrolytic breakage of the lactam C(O)-N link to liberate the carbasugar and install the desired pseudo-anomeric amine and the hydroxymethyl or carboxyl functionalities. The sequences leading to trans-configured carbafuranosyl compounds 1 and 5 and carbapyranosyl compounds 3 and 7 were 12- and 13-step processes, with overall yields of 34%, 35%, 17%, and 16%. Cis-configured isomers 2, 4, 6, and 8 were obtained only in minor yields.

5-Hydroxyalkyl derivatives oftert-butyl 2-oxo-2,5-dihydro-1H-pyrrole-1-carboxylate: diastereoselectivity of the Mukaiyama crossed-aldol-type reaction

“…When a larger aldehyde was used, as in the case of compounds (II) and (III), the relative stereochemistry of the newly created chiral centres is R,S. The synthetic procedure used led to a syn configuration of the two newly created chiral centres in all three compounds, in close analogy to reports in the literature (Battistini et al, 2004;Rassu et al, 2002Rassu et al, , 2003Casiraghi et al, 1992). Changing the Lewis acid, that is using BF 3 instead of SnCl 4 , and introducing an aryl substituent at the carbon next to the nucleophilic centre, does not influence the diastereoselectivity of the process.…”

“…The relative configuration at the two newly formed chiral centres could not be determined unequivocally using NMR methods. A literature search showed that the Bocprotected (Boc is tert-butoxycarbonyl) (tert-butyldimethylsilyloxy)pyrrole (1) had been used in a series of very elegant natural product syntheses (Battistini et al, 2004;Rassu et al, 2002Rassu et al, , 2003; Barnes et al, 2002;Casiraghi et al, 1992;DeGoey et al, 2002). The diastereoselectivity of the reaction with a series of chiral aldehydes and imines has been carefully studied and was shown, for most of the reported processes, to be syn.…”

Further Uses of Pyrrole‐Based Dienoxysilane Synthons: A Full Aldol Approach to Azabicyclo[x.2.1]alkane Systems

“…Recent notable achievements in this area include, for example, the enantioselective synthesis of the (20 S ) proteasome inhibitor (+)‐lactacystin ( 1 ) developed by Baldwin and co‐workers,2a the discovery of the potent influenza virus neuraminidase inhibitor A‐315675 ( 2 ) by researchers at the Abbott group,2b,2ethe stereoselective access to the pentacyclic alkaloid (–)‐cephalotaxine ( 3 ) by Royer and co‐workers2c and thestereocontrolled entry to a collection of hydroxylatedcarbocyclic amines and amino acids, as exemplified by structure 4 , developed by us (Figure 1). 2d,2f–2i…”

The Vinylogous Mukaiyama Aldol Reaction in Natural Product Synthesis

“…Pure d-erythro-C18-sphingosine precursor (324) was isolated in 75% yield along with a small amount of 323 (13%). This technique, namely, the VMAR between 2,3-O-isopropylidene-dglyceraldehyde ent-56 with TBSOP (315) in the presence of SnCl 4 was also exploited for the assembly of the amino carbon backbone in a divergent synthesis of two carbafuranosylamines, two carbapyranosylamines, two carbafuranosylamino acids, and two carbapyranosylamino acids (not shown) [131]. The total synthesis of 2,4-diamino-2,4-dideoxy-α,β-l-arabinopyranose (328), the azasugar component of the naturally occurring antifungal antibiotic prumycin [132,133] commenced with the coupling of TBSOP (315) to enantioenriched isopropylidene-protected l-serinal (326) (93-95% ee).…”