Marcello Di Giacomo

Camphor-derived 2-stannyl-N-Boc-1,3-oxazolidine: A new chiral formylanion equivalent for the asymmetric synthesis of 1,2-diols

Abstract Optically pure 2-tributylstannyl-N-Boc-1,3-oxazolidine 6 , prepared from the camphor-derived aminoalcohol 5 , was converted to diastereomerically pure 2-acyl derivatives 8 in three steps. Reaction of these ketones with Grignard reagents at −78°C proceeded with high stereoselectivity affording tertiary carbinols which gave 1,2-diols with >96% ee after hydrolysis and reduction of the intermediate α-hydroxy aldehydes. A new deblocking procedure of the t-Boc group is also described.

CONFORMATIONALLY CONSTRAINED DIPEPTIDES : SYNTHESIS OF 7,5- AND 6,5-FUSED BICYCLIC LACTAMS BY STEREOSELECTIVE RADICAL CYCLIZATIONS

Abstract A study of radical cyclizations of β-substituted α-N-acetyl acrylamide have been performed: high level of regio- and stereoselectivity was obtained.

Chiral 2-lithio-13-dioxolanes and -2-lithiooxazolidines: New formyl anion equivalents

Abstract The preparation of enantiomerically pure 2-lithio-1,3-dioxolanes and 2-lithiooxazolidines and their use as formyl anion equivalents in addition reactions to aldehydes are described.

Synthesis of new bicyclic lactam peptidomimetics by ring-closing metathesis reactions

Abstract An efficient and versatile synthetic method for the preparation of new fused bicyclic lactams 3a and 3b is described. The spirane cyclopentane nucleus was easily installed by diallylation of the pyroglutamate derivative 18 followed by ring-closing metathesis (RCM). A more practical and stereoselective method for the allylation of the α-methoxy carbamate 21 , involving the use of InCl3 as a Lewis acid, was developed. In the crucial coupling reaction of the diastereomeric mixture of cis- and trans-pirrolidine derivatives 5a and 5b with N-Cbz vinyl phenylalanine only the cis isomer was found to react. An RCM reaction on the dipeptides 25a and 25b followed by catalytic hydrogenation, gave the final epimeric bicyclic lactams 3a and 3b . The same synthetic sequence on the model compound 7 , lacking the spiro cyclopentane nucleus, is also reported.

Practical stereoselective synthesis of conformationally constrained unnatural proline-based amino acids and peptidomimetics

Abstract A practical synthetic scheme was developed to prepare both the cis- and trans-fused stereoisomers of N-Boc- l -octahydroindole-2-carboxylic acid ( l -Oic) methyl ester. Key event of the synthetic sequence was the ring-closing metathesis of a suitable diallylated proline derivative. This is the first reported practical synthesis of the trans-fused isomer. Functionalization of the octahydroindole nucleus by electrochemical oxidation followed by acid-catalysed allylation paved the way for the preparation of reverse-turn dipeptide mimics.

Synthesis of 7,5-fused bicyclic lactams by stereoselective radical cyclization

Abstract 7,5-Fused bicyclic lactams of type 1 were synthesised by a route involving the radical cyclization of the intermediate 2 . High level of stereoselection was obtained in this reaction.

Practical stereoselective synthesis of α-d-C-mannosyl-(R)-alanine

Abstract α- d - C -Mannosyl-( R )-alanine 2 was synthesized in only four steps starting from the known acetonide protected d - ribo -hex-1-enitol 4 and N -benzoylalanine. The key C–C bond formation between the sugar and the amino acid moieties was effected through a Claisen rearrangement of the intermediate oxazole 7 , derived from the ester 6 .

A novel chiral synthetic equivalent of glyoxal and its application to the asymmetric synthesis of O-protected α-hydroxy aldehydes

Abstract Diastereomerically pure 2-formyl-N-Boc-1,3-oxazolidine 7 was prepared in 83% yield from stannyloxazolidine 4. Grignard additions to the formyl group of compound 7 in the presence of Lewis acids afforded diastereomerically pure secondary carbinols 8. Protection of the hydroxyl group and unmasking of the oxazolidine ring gave O-protected α-hydroxy aldehydes 11, which were immediately reduced to the corresponding 1,2-diols 12.

Stereoselective synthesis of 6,5-bicyclic reverse-turn peptidomimetics

Abstract A flexible stereoselective synthetic scheme was developed to prepare 6,5-fused bicyclic lactams, that molecular mechanics calculations revealed to have a potential as reverse-turn mimetics. The convergence of the synthetic sequence was achieved by attachment of a properly substituted malonate unit to the (2S)-cis-5-(2-hydroxyethyl)proline tert-butyl ester. Stereoselective intramolecular alkylation of the malonate afforded the 6-membered lactam fused to the 2-carbalkoxy pyrrolidine nucleus. X-ray diffraction analysis of a more advanced synthetic derivative allowed the unequivocal assignment of the configuration at the newly created quaternary stereocenter as R.

Stereoselective Pd-catalyzed synthesis of quaternary α-D-C-mannosyl-(S)-amino acids.

In this paper, we report the stereoselective synthesis of α-D-C-mannosyl-(S)-amino acids exploiting, as a key step, an allylic alkylation of glycal-derived π-allyl Pd(II) intermediates, prepared by oxidative addition of Pd(0) species to 2,3-unsaturated pyranosides (pseudoglycals). The reaction of 4,6-di-O-acetyl α-pseudoglucal carbonate 10a with racemic alanine-, valine-, and phenylalanine-derived azlactones gave the corresponding (4S)-4-α-D-C-mannosyl-2-phenyloxazol-5(4H)-ones as the major diastereoisomers in high yields. The final α-D-C-mannosyl-(S)-amino acids were obtained in a few steps comprising highly diastereoselective dihydroxylation of the glucal derivative double bond followed by the one-pot hydrolysis of the benzamido and acetate protecting groups. Main features of this method are the conciseness of the synthetic sequence, the high diastereoselection of the allylic alkylation step, the use of racemic α-amino acids as starting material, and the good overall yields.