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A total asymmetric synthetic approach to (-)-yohimbane and ent-alloyohimbane which employs a novel aziridine-allylsilane cyclization reaction as a key step in the synthesis to form the E ring is described. Optically pure aziridine-allylsilane were treated with BF3*OEt2 and provided a mixture of aminomethyl substituted carbocycles in high yield and modest diastereoselectivity. The lactam was formed from alkylation of the tosylamide followed by oxidation of the olefin, and was converted to (-)-yohimbane and ent-alloyohimbane via a Bischler-Napieralski reaction. The synthesis was accomplished in eight steps and 24% overall yield.

The synthesis of (-)-bestatin and its analogues has been undertaken through a new method. Bestatin and its analogues are naturally occurring small peptides with a nonproteinogenic alpha-hydroxy-beta-amino acid at the N-terminus of the peptide chain. The novel technique uses an intramolecular acylnitrene-mediated aziridination to produce a key bicyclic aziridine in excellent yield and stereoselectivity. The aziridine can be opened by using organometallic reagents to produce a series of substituted oxazolidinones. The latter compounds can be easily transformed to bestatin and its analogues.

A novel method of synthesizing vicinal amino alcohols through a tandem ring opening of acylnitrene aziridination-aziridine was designed. The design featured an intramolecular aziridination reaction to form a bicyclic aziridine which was then reacted with the desired nucleophile to produce vicinal amino alcohols. It was found that the nucleophilic attack occurred only at the least substituted carbon of the aziridine ring.

A novel method for the preparation of enantiomerically pure monosubstituted aziridines was developed based on the reaction of an aziridine tosylate with a primary organocuprate reagent. The synthetic strategy was characterized by the formation of ring-opened intermediates due to the attack of cuprate to the least-substituted carbon of the aziridine ring. Subsequent ring closure of the intermediates via displacement of the tosyl ester in the presence of chiral solvating agents led to the formation of the aziridines.

Synthesis of (1R,3R,5S)-1-amino-3-(hydroxymethyl)bicyclo(3.1. 0)hexane from (2S,3S)-2-amino-2,3-methanoadipate involves cyclization, elimination, reduction and hydrogenation. Conversion of (R)-2-((benzyloxy)ethyl)oxiranes to (2S,3S)-2-amino-2,3-methanoadipate involves the use of lactones. The bicyclo(3.1.0)hexane functions as a precursor in the synthesis of various carbocyclic nucleosides.

A study reveals the intramolecular cyclization of an ester enolate to a timulated aziridine, which is a part of a new technique of preparing an important precursor of carbocyclic nucleoside (1S, 3R)-1-amino-3-(hydroxymethyl)cyclopentane, as a result of which a substituted cyclopentane ring is formed. The intermediary of the bicyclic lactam ensures that a cyclopentane, which was formed as a mixture of diasteromers, was transformed to a single diasteromer.

A new method for the synthesis of (1S,3R)-1-amino-3-(hydroxymethyl)cyclopentane, a precursor in the synthesis of some carbocyclic nucleoides, is discussed. The method includes three steps: the synthesis of (S)-2-aminoadipic acid; Dieckmann cyclization to an aminocyclopentanone; and derivatization of (1S,3R)-1-amino-3-(hydroxymethyl)cyclopentane. The importance of carbocyclic nucleotides lie in their antiviral and antineoplastic properties.

N-benzyl-L-glutamic acid provides the substrate in the enantioselective 12-step synthesis of natural (-)-slaframine and two indolizidine analogues, (-)-1,8a-diepislaframine and (-)-8a-epidesacetoxyslaframine. The alkaloid causes the black patch disease in ruminants but is a potential drug against cholinergic dysfunction. A key step in the synthesis involves the reductive double cyclization of the azido epoxy tosylate to yield the indolizidine skeleton, which is converted in two steps to slaframine. Its absolute configuration is established as 1S,6S,8aS by NMR studies.

Abstract This paper reports a systematic study of the level of flavan-3-ol monomers during typical processing steps as cacao beans are dried, fermented and roasted and the results of Dutch-processing. Methods have been used that resolve the stereoisomers of epicatechin and catechin. In beans harvested from unripe and ripe cacao pods, we find only (-)-epicatechin and (+)-catechin with (-)-epicatechin being by far the predominant isomer. When beans are fermented there is a large loss of both (-)-epicatechin and (+)-catechin, but also the formation of (-)-catechin. We hypothesize that the heat of fermentation may, in part, be responsible for the formation of this enantiomer. When beans are progressively roasted at conditions described as low, medium and high roast conditions, there is a progressive loss of (-)-epicatechin and (+)-catechin and an increase in (-)-catechin with the higher roast levels. When natural and Dutch-processed cacao powders are analyzed, there is progressive loss of both (-)-epicatechin and (+)-catechin with lesser losses of (-)-catechin. We thus observe that in even lightly Dutch-processed powder, the level of (-)-catechin exceeds the level of (-)-epicatechin. The results indicate that much of the increase in the level of (-)-catechin observed during various processing steps may be the result of heat-related epimerization from (-)-epicatechin. These results are discussed with reference to the reported preferred order of absorption of (-)-epicatechin > (+)-catechin > (-)-catechin. These results are also discussed with respect to the balance that must be struck between the beneficial impact of fermentation and roasting on chocolate flavor and the healthful benefits of chocolate and cocoa powder that result in part from the flavan-3-ol monomers.

A method using a tert-butyl ester as a catalyst was developed to remove the N-BOC protecting group, the removal being essential for several synthetic sequences. Dry HCl in ethyl acetate enhanced the selective removal of the N-BOC protecting group. Different protecting groups that shared common characteristics exhibited small differences with respect to acid cleavage.

A new synthesis method is described for the aziridine required for the aziridine-[pi]-nucleophile cyclization for preparing 6-azabicyclo[3.2.1]octanes. The studies have shown that N-diphenylphospinyl and N-H aziridines have not led to the desired bicyclic ring systems, whereas a nosyl group on the aziridine nitrogen has led to the bicyclic ring system.

Synthetic or natural aza-sugars offer a good therapeutic approach to a variety of disease states by acting as transition state mimics to sugar processing enzymes. A study reports the facile synthesis of polyhydroxylated 2-azabicyclo[3.2.1]octane that can be selectively functionalized.