Amino acids alkaloids preparation

These biological activities, combined with the use of these products as starting materials to prepare a- and p-amino acids, alkaloids, heterocycles, taxoids, and other types of compounds of biological and medicinal interest [39—4-7], provide the motivation to explore new methodologies for the synthesis of substances based on the p-lactam core. 

As shown in Table 26, the same selectivities were observed in the reactions of other 3-acyl-l,3-oxazolidin-2-ones. Thus, by using the same chiral source ((R)-(+)-binaphthol), both enantiomers of the Diels-Alder adducts between 3-acyl-l,3-oxazolidin-2-ones and cyclopentadiene were prepared. Traditional methods have required both enantiomers of chiral sources in order to prepare both enantiomers stereoselectively [74], but the counterparts of some chiral sources are of poor quality or are hard to obtain (for example, sugars, amino acids, alkaloids, etc.). It is noted that the chiral catalysts with reverse enantiofacial selectivities could be prepared by using the same chiral source and a choice of achiral ligands. 

The structure of the un-named alkaloid (19) obtained from a Thermoac-tinomyces strain has been confirmed by a simple synthesis from tryptamine and the thiazole amino-acid (20), prepared from (+)-(5)-alanine (Scheme 2). ... 

Small chiral molecules. These CSPs were introduced by Pirkle about two decades ago [31, 32]. The original brush -phases included selectors that contained a chiral amino acid moiety carrying aromatic 7t-electron acceptor or tt-electron donor functionality attached to porous silica beads. In addition to the amino acids, a large variety of other chiral scaffolds such as 1,2-disubstituted cyclohexanes [33] and cinchona alkaloids [34] have also been used for the preparation of various brush CSPs. 

Kibayashi and coworkers have used enantiometrically pure allylic silyl ethers obtained from amino acids in cycloaddition with nitrones (Eq. 8.49).71 Cyclic nitrone reacts with a chiral allyl ether to give selectively the exo and erythro isomer (de 90%). Optically active alkaloids containing a piperidine ring such as (+)-monomorine,71c (+)-coniine,71a and (-)-oncinotine71b have been prepared from the addition product. 

At that time, as now, the enantiomers of many chiral amines were obtained as natural products or by synthesis from naturally occurring amines, a-amino acids and alkaloids, while others were only prepared by introduction of an amino group by appropriate reactions into substances from the chiral pool carbohydrates, hydroxy acids, terpenes and alkaloids. In this connection, a recent review10 outlines the preparation of chiral aziridines from enantiomerically pure starting materials from natural or synthetic sources and the use of these aziridines in stereoselective transformations. Another report11 gives the use of the enantiomers of the a-amino acid esters for the asymmetric synthesis of nitrogen heterocyclic compounds. 

Peptide derivatives of the bisindole alkaloids have been prepared by appending amino acids at C-3. Reaction of acylazide 62 with an ct-amino acid ester affords amide derivatives of this type (122) (46). Conversely, the attachment of the amino acid can be inverted by reacting a C-3 amide derivative with an activated amino acid ester. Thus, treatment of 3-0-aminoethyl)-4-deacetylvinblastine amide (70) with an N-protected a-ami-noacylazide gives the alternative amide derivative (123). These techniques have been used to prepare di-, tri-, and tetrapeptide conjugates. 

CMPA, CE MEKC CSP e.g. cyclodextrins, amino acids cholic acids, tartaric acids, alkaloids etc. and Derivatives Thereof analytical to preparative excellent, fair to moderate... 

Recent developments regarding the utility of chiral amino acids in asymmetric synthesis of natural products were reported. Examples of such syntheses are the preparation of carbohydrates from (S)-glutamic acid 257), (S)-alanine 258), or (S)-threonine 259), and syntheses of alkaloids 260), terpenes 26I), peptide 262) derivatives, and toxines 263>. 

These alkaloids contain pyrrole or modified pyrrole, e.g. pyrrolidine, ring system. The simplest example of this class is nicotine. A pyrrolidine ring is the central structure of the amino acids proline and hydroxyproline. These alkaloids are also found in many drug preparations, e.g. procyclidine hydrochloride, which is an antichohnergic drug mainly used for the treatment of drug-induced Parkinsonism, akathisia and acute dystonia. 

The a-methoxylated derivatives are shown to be versatile synthons because of the reactivity of the methoxy group near the nitrogen atom, a-Methoxycarbamates, prepared by anodic oxidation, were used as key intermediates in the synthesis of a-amino acids,200 a new carbon-phosphorus bond-forming reaction,200 and in a new method of acylation of aliphatic amines at the -position.201 The application of this reaction to the synthesis of pyrrolidine, piperidine, and tropane alkaloids is also described.202... 

Important indole derivatives (see Scheme 2) include (i) indigo, a vat dye known and widely used since antiquity, and originally obtained from indican, a (3-glucoside of indoxyl which occurs in some plants. Indigo is now prepared synthetically. Tyrian purple, a natural dye used since classical times, is 6,6 -dibromoindigo (ii) the numerous indole alkaloids, with complex derivatives such as yohimbine and strychnine (iii) tryptophan, an essential amino acid found in most proteins. Its metabolites include skatole and tryptamine and (iv) 3-indoleacetic acid, which is important as a plant growth hormone. 

IV-alkyl and IV-acyl derivatives has been widely used, the method of choice is that of trimethylsilylation. The procedure is widely applicable to natural products (e.g. carbohydrates, amino acids, steriods, alkaloids, polyhydroxyphenols, fatty acids, etc.), and has found great use in analytical and preparative laboratories which handle such compounds. 

The asymmetric aziridination of a, P-unsaturated carboxylic acid derivatives is a direct route to optically active aza-cyclic a-amino acids, and this class of chiral aziridines can also be used as chiral building blocks for the preparation of other amino acids, P-lactams, and alkaloids. Prabhakar and coworkers carried out an asymmetric aziridination reaction of tert-butyl acrylate with O-pivaloyl-N-arylhydroxylamine 25 in the presence of cinchonine-derived chiral ammonium salt 2e under phase-transfer conditions, which furnished the corresponding chiral N-arylaziridine 26 with moderate enantioselectivity (Scheme 2.24) [46],... 

In particular, it is not only the cinchona alkaloids that are suitable chiral sources for asymmetric organocatalysis [6], but also the corresponding ammonium salts. Indeed, the latter are particularly useful for chiral PTCs because (1) both pseudo enantiomers of the starting amines are inexpensive and available commercially (2) various quaternary ammonium salts can be easily prepared by the use of alkyl halides in a single step and (3) the olefin and hydroxyl functions are beneficial for further modification of the catalyst. In this chapter, the details of recent progress on asymmetric phase-transfer catalysis are described, with special focus on cinchona-derived ammonium salts, except for asymmetric alkylation in a-amino acid synthesis. 

Cinchona alkaloids, of course, have occupied the central position in the design of chiral PTCs. By employing a simple chemical transformation of the tertiary amine ofthe natural cinchona alkaloids to the corresponding quaternary ammonium salts, using active halides (e.g., aryl-methyl halides), a basic series of PTCs can be readily prepared. Cinchona alkaloid-derived PTCs have proved their real value in many types of catalytic asymmetric synthesis, including a-alkylation of modified a-amino acids for the synthesis of higher-ordered a-amino acids [2], a-alkylation of... 

The solid-phase synthesis of a-amino acids via alkaloid-catalyzed alkylation has been investigated by the O Donnell group [64, 65]. The solid-phase based synthetic approach is particularly useful for rapid preparation of a-amino acids for combinatorial application. The concept of this solid-phase synthetic approach, which comprises three key steps, is shown in Scheme 3.22 (for formation of (R) enantiomers). First, solid-phase bound glycine, 51, is converted into its benzophenone imine de-... 

Deng et al. reported in 2001 that a wide variety of N-urethane-protected N-carboxy anhydrides such as, for example, rac-18 shown in Scheme 13.9 undergo kinetic resolution when treated at low temperature with alcohols in the presence of dimeric cinchona alkaloids such as (DHDQ)2AQN, 11 [20], The N-carboxy anhydrides rac-18 were prepared from the racemic amino acids rac-17 by a two-step procedure involving cyclization with diphosgene and subsequent N-protection with, e.g., Cbz or Fmoc. The kinetic resolution of rac-18 proceeded with excellent... 

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