Jaime Escalante

Synthesis of β-lactams and cyclo-β-dipeptides from β-amino acids: experimental observations and theoretical analysis

Abstract The cyclization of β-amino acids by means of activating agents is one of the most useful approaches for the construction of β-lactams; however, we found that when PhP(O)Cl2 (in Et3N) is employed as the activating agent, cyclization of the derived ‘active ester’ affords varying amounts of cyclo-β-dipeptides, depending on reactions conditions (solvent, temperature, and concentration), as well as on the substitution pattern in the starting β-amino acid. Theoretical rationalization of the experimental results was achieved by modeling studies of the presumed intermediates, both at semi-empirical (MNDO, AM1, and PM3) and at ab initio (HF/3-21G) levels. In the latter calculations, simulation of solvents was accomplished by means of self-consistent reaction field theory (Onsager’s method).

Michael Additions of Amines to Methyl Acrylates Promoted by Microwave Irradiation

A simple and efficient protocol has been developed for the Michael addition of amines to α,β-unsaturated esters under microwave irradiation. Under these conditions there was a significant decrease in the reaction time, increases in the yields and increased purity of the products.

Efficient Microwave Assisted Syntheses of 2,5-Diketopiperazines in Aqueous Media

Aqueous in situ one-pot N-Boc-deprotection-cyclization of Nα-Boc-dipeptidyl-tert-butyl and methyl esters under microwave irradiation afforded 2,5-diketopiperazines (DKPs) in excellent yields. This protocol is rapid, safe, environmentally friendly, and highly efficient, and showed that the tert-butoxy moiety is also an excellent leaving group for these cyclizations.

Hydroxylation of the diterpenes ent-kaur-16-en-19-oic and ent-beyer-15-en-19-oic acids by the fungus Aspergillus niger.

The diterpenes ent-kaur-16-en-19-oic acid (1) and ent-beyer-15-en-19-oic acid (2) are the major constituents of a spasmolytic diterpenic mixture obtained from the roots of Viguiera hypargyrea, a Mexican medicinal plant. Microbial transformation of 1 and 2 was performed with Aspergillus niger. Two metabolites, ent-7alpha,11beta-dihydroxy-kaur-16-en-19-oic acid (4) and ent-1beta,7alpha-dihydroxy-kaur-16-en-19-oic acid (5), were isolated from the incubation of 1, and one metabolite, ent-1beta,7alpha-dihydroxy-beyer-15-en-19-oic acid (6), was isolated in high yield (40%) from 2. The structures were elucidated on the basis of spectroscopic analyses and confirmed by X-ray crystallographic studies. Compounds 1-4 and 6 and methyl ester derivatives 4a and 6a were evaluated for their ability to inhibit the electrically induced contraction of guinea-pig ileum. Compounds 1, 3, 4, 4a and 5 were significantly active. These results showed that dihydroxylation of 1 at 7beta, 11alpha-, and 1alpha, 7beta-positions resulted in a loss of potency.

NMR and X-ray crystallographic studies of axial and equatorial 2-ethoxy-2-oxo-1,4,2-oxazaphosphinane

Condensation of (S)-(N-benzyl)-phenylglycinol with formaldehyde in the presence of diethylphosphite afforded hydroxy- aminophosphonate (S)-3, which upon treatment with KH yielded a 97:3 mixture of the interesting, phosphorus-containing 2-ethoxy-2-oxo- 1,4,2-oxazaphosphinanes (2S,5S)-1 and (2R,5S)-1. Suitable crystals of both diastereomers were used in X-ray crystallographic studies that permitted unequivocal configurational assignment, as well as examination of the consequences of nO!s P-O stereoelectronic interactions on

Synthesis of γ-Nitro Aliphatic Methyl Esters Via Michael Additions Promoted by Microwave Irradiation

A simple and efficient protocol has been developed for the direct synthesis of γ-nitrobutyric acid methyl esters under microwave irradiation. This methodology reduces reaction times from days to minutes, compared to conventional conditions. Additionally, these conditions increased yields and provided cleaner reactions.

Synthesis, resolution and absolute configuration of trans 4,5-diphenyl-pyrrolidin-2-one: a possible chiral auxiliary

Abstract β-Lactam (±)-N-benzyl-4-phenyl-azetidin-2-one rac-6a was converted into the γ-lactam (±)-trans-4,5-diphenyl-pyrrolidin-2-one rac-5 which was resolved via the preparation of diastereomers with N-phthalyl- l -alanine chloride or d -alanine chloride and its absolute configuration was determined by X-ray crystallographic analysis. This heterocycle has potential as a chiral γ-lactam in asymmetric induction due to the steric effects of its phenyl groups.

“Alternative method for the resolution of 1-benzoyl-2-tert-butyl-3-methyl-1,3-imidazolidin-4-one”

Abstract The title heterocycles, which are useful chiral precursors for the asymmetric synthesis of α-amino acids, can be prepared in enantiomerically pure form via the separation of diastereomeric derivatives incorporating (S)-α-methyl-benzylamine.

Synthesis of 2,3-Dihydro-4(1H)-quinazolinones

An improved procedure for the synthesis of 2-substituted 2,3-dihydro-4(1H)-quinazolinones through diastereomer separation of the corresponding quinazolinones derivatives is presented. The determination of their absolute configurations was obtained by X-Ray diffraction.

DIRECT HALOGENATION REACTIONS IN 2,3-DIHYDRO-4(1H)-QUINAZOLINONES

Reaction of 2,3-dihydro-4(1H)-quinazolinones with NBS, Br2/Et3N and NCS yields 6,8-Br/Cl-2,3-dihydro-4(1H)-quinazolinones with moderate to good yield. The method does not require a catalyst and offers extremely short reaction time. INTRODUCTION 2,3-Dihydro-4(1H)-quinazolinones form an important class of bioactive compounds and these can easily be oxidized to their quinazolin-4(3H)-one analogues. 1 In general, the derivatives of the quinazolinones are considered as an important building blocks 2 for a large number of diverse alkaloids 3 and present a wide range of biological and pharmaceutical activities. 4 In addition, numerous efforts of synthesis have been made to obtain halogenated quinazolinones for their pharmacophoric effect. 5 For example, the incorporation of a fluorine or chlorine atom into an active compound results in beneficial changes in molecular properties such as higher fat solubility giving different absorption and transport rate, altered electronic effects, improved stability, and equivalent steric size. 6 On the other hand, quinazolinones halogenated with bromine have shown their importance as building blocks in the synthesis of compounds with biological activity. 7 In the literature, to obtain halogenated quinazolinones one first treats anthranilic acid (a) with bromine in presence of acetic acid or sulfuryl chloride to form the monoand di-halogenated derivatives b and c, HETEROCYCLES, Vol. 85, No. 9, 2012 2173