Narciso M. Garrido

Asymmetric syntheses of β-phenylalanine, α-methyl-β-phenylalanines and derivatives

A strategy of highly stereoselective conjugate additions of lithium (R)-(α-methylbenzyl)benzylamide to tert-butyl cinnamate and its 2-methyl derivative combined with appropriate tandem or sequential electrophilic quenches allows the asymmetric syntheses of β-phenylalanine (95% enantiomeric excess) and homochiral (2R, 3S)- and (2S, 3S)-α-methyl-β-phenylalanine and the corresponding β-lactams (3R, 4S)- and (3S, 4S)-3-methyl-4-phenylazetidinones.

Cyclic β-amino acid derivatives: synthesis via lithium amide promoted tandem asymmetric conjugate addition–cyclisation reactions

The product distribution upon conjugate addition of homochiral lithium N-benzyl-N-alpha-methylbenzylamide to dimethyl-(E,E)-nona-2,7-dienedioate can be controlled to give either the cyclic 1,2-anti-1,6-anti-beta-amino ester (derived from conjugate addition and intramolecular enolate cyclisation) or the acyclic bis-beta-amino ester derivative (derived from double conjugate addition) in high de. The introduction of a protected nitrogen functionality into the diester skeleton facilitates, after conjugate addition and intramolecular enolate cyclisation, the asymmetric construction of piperidines in high de; variation in the N-protecting group indicates that the highest stereoselectivity is observed with alpha-branched N-substituents. Tandem conjugate addition-aldol reactions can also be achieved stereoselectively, with lithium amide conjugate addition to epsilon- and zeta-oxo-alpha,beta-unsaturated esters giving the corresponding five and six membered cyclic beta-amino esters in high de. N-deprotection by hydrogenolysis of the products arising from these reactions furnishes a range of polyfunctionalised transpentacin and transhexacin derivatives in high de and ee.

Preparation of methyl (1R,2S,5S)- and (1S,2R,5R)-2-amino-5-tert-butyl-cyclopentane-1-carboxylates by parallel kinetic resolution of methyl (RS)-5-tert-butyl-cyclopentene-1-carboxylate.

Comparison of the kinetic and parallel kinetic resolutions of methyl (RS)-5-tert-butyl-cyclopentene-1-carboxylate allows for the efficient synthesis of both (1R,2S,5S)- and (1S,2R,5R)-enantiomers of methyl 2-amino-5-tert-butyl-cyclopentane-1-carboxylate.

A diterpene alcohol from Halimium viscosum

Abstract A hexane extract of Halimium viscosum collected at La Fregeneda (Salamanca, Spain) yielded a new diterpene alcohol, tormesol. Its structure was determined by chemical transformations and NMR spectroscopy with 1 H 1 H (COSY), 13 C 13 C (2D-inadequate) and 1 H 13 C (one bond and long range correlations) two-dimensional experiments.

Conjugate addition to (α,β)(α′,β′)-diendioate esters by lithium (α-methylbenzyl)benzylamide: tandem addition–cyclisation versus double addition

Abstract Strategies for obtaining either the products from tandem conjugate addition–cyclisation or from double addition in the highly stereoselective addition of lithium ( R )-(α-methylbenzyl)benzylamide to (α,β)(α′,β′)-diendioate esters are demonstrated.

ASYMMETRIC SYNTHESIS OF (R)- AND (S)-METHYL (2-METHOXY-CARBONYLCYCLOPENT-2-ENYL)ACETATE AND (R)- AND (S)-2-(2-HYDROXY-METHYL-CYCLOPENT-2-ENYL)ETHANOL

Abstract ( R )- and ( S )-Methyl (2-methoxycarbonylcyclopent-2-enyl)acetate 1 and ( R )- and ( S )-2-(2-hydroxymethyl-cyclopent-2-enyl)ethanol 2 have been obtained from dimethyl (E,E)-octa-2,6-diendioate 3 by a diastereoselective tandem conjugate addition protocol, from ( R )- and ( S )-lithium (α-methylbenzyl)benzylamide 4 respectively.

Chemistry of zamoranic acid. Part IX homochiral synthesis of polygodial and warburganal from 17-acetoxy-7-labden-15-ol

Abstract 14,15-di nor -17-acetoxy-7-labden-13-one, 4 was prepared from zamoranic acid methyl ester 5 . Photochemical cleavage of 4 gave 12-acetoxy-7,9(11)-drimadiene, 3 , in 75% overall yield. The chemo- and diastereoselective epoxidation of 3 afforded 12-acetoxy-9α and 9β(11)-epoxy-7-drimene, 17 and 18 in 4:1 ratio. Ring-opening of 17 (or the mixture 17 18 ) using BF 3 ·Et 2 O or ring-opening of the mixture 17 18 lead to the synthetic precursor of polygodial: (9 R )-12-acetoxy-drimen-11-al, 20 , with a 90% diastereoisomeric excess. The chemo- and diastereoselective cis -hydroxylation of diene 3 led to the synthetic precursor of warburganal 9α,11,12-trihydroxy-7-drimene, 29 with 47% yield. Polygodial and warburganal were prepared from zamoranic acid methyl ester in 55 and 27% overall yield, respectively.

Enantioselective Organocatalytic Reactions with Isatin

The authors gratefully acknowledge FSE, MICINN CTQ2009-11172BQU, Junta de Castilla and Leon (SA162A12-1) for financial support. MFF is grateful to the JCyL-ESF for her FPI fellowship. JP is grateful to MINECO for a FPU fellowship. P.G-G. is grateful for a JAE-DOC contract from CSIC co-funded by the European Social Fund (ESF)

Diastereoselective synthesis of delta-aminoacids through domino Ireland-Claisen rearrangement and Michael addition.

A novel domino reaction--stereoselective Ireland-Claisen rearrangement and asymmetric Michael addition--is described. A protocol starting from Baylis-Hillman adducts 3a-f using chiral lithium amide affords optically active gamma-substituted delta-amino acids 4a-f with high diastereoselectivities and enantioselectivities. The acid can be isolated easily from large-scale reactions and transformed to 2,3-disubstituted piperidines 11 or 2-substituted nipecotic acid derivates 12.

Diterpenoid and other components of Cistus laurifolius

Abstract From the ethanol extract of C. laurifolius was isolated a new diterpene, 6β,8-dihydroxy- ent -13 E -labden-15-oic acid, which we called laurifolic acid. Four glucosides were separated in the form of their acetyl derivatives: β- D -glucopyranosiloxyethane, 4-β- D -glucopyranosiloxyacetophenone, roseoside and 1,3-dihydroxy-5-β- D -glucopyranosiloxybenzene. An inositol, 1- O -methyl-epi-inositol, was also identified.