Bioactive compound synthesis

Scheme 9.14 Epoxidation of aliphatic alkenes and applications in bioactive compound synthesis.

Indenoindoles and cyclopentacarbazoles as bioactive compounds Synthesis and biological appHcations 13EMC(69)465. 

La Ferla, B., Orsato, A., Zona, C., Cervi, G., Papeo, G., Felder, F.R., and Nicotra, F. (2010) Synthesis of a 3-carboline scaffold properly functionalized for the generation of libraries of bioactive compounds. Synthesis, 4, 601-604. 

The esters of thiosulfinic acid R -SO,-S-R are used as fungicides and antibacterial prepai ations. These compounds have similar stiaicture fragments to allicin - natural insecticide from garlic with following structure (CH =CH-CH ),[SO-S] (http //www.ALLICIN.com). For deter-mination of ethyl S-ester of 4-aminobenzenthiosulfinic acid (esulan) in the ointment RP-HPLC was proposed [1] with acetonitrile water=30 70 as eluent. For seai ching bioactive compounds the synthesis of new esters of thiosulfinic acid is perspective that was confirmed by results of recent studies as instance [2]. Therefore requirements ai e existed for investigation HPLC sepai ations of these substances. 

These thiazoles are of specific interest in that they display exceptional pharmacological properties. Additionally, the unsaturated 2-aminonitrile functionality of the above thiazoles is recognized for its versatile functionality and therefore for its ensuing significance in the synthesis of heterocycles. The synthetic utility of thiazoles 13a-f is illustrated by the reactions of the unsaturated 2-aminonitrile functionality in compounds 13b and 13c with formamidine acetate, resulting in the thiazolopyrimidines 14a and 14c respectively. The synthesis of this relatively rare family of heterocycles provides a route into structurally similar bioactive compounds. ... 

Combinatorial synthesis of multicomponent mixtures, among them mixtures of heterocycles, for screening of bioactive compounds 99JMC3743. 

Development of base-catalyzed Diels-Alder reaction of 3-hydroxy-2-pyrone and its application to synthesis of bioactive compounds 99YGK84. 

Fluorination of O- and N-heterocycles with molecular fluorine in the synthesis of fluorine-containing bioactive compounds 98YGK107. 

Both chiral lactones and ketones have been utilized in asymmetric synthesis of bioactive compounds like lipoic acid [175[ and natural products like various insect pheromones [176[. 

Biocatalytic access to both antipodal sulfoxides was exploited in total syntheses of bioactive compounds, which is outlined in some representative examples. Biooxidation of functionalized dialkyl sulfides was utilized in the direct synthesis of both enantiomers of sulforaphane and some analogs in low to good yields and stereoselectivities (Scheme 9.27) [206]. This natural product originates from broccoli and represents a potent inducer of detoxification enzymes in mammalian metabolism it might be related to anticarcinogenic properties of plants from the cruciform family. All four possible stereoisomers of methionine (R = Me) and ethionine sulfoxides... 

Enantioenriched alcohols and amines are valuable building blocks for the synthesis of bioactive compounds. While some of them are available from nature s chiral pool , the large majority is accessible only by asymmetric synthesis or resolution of a racemic mixture. Similarly to DMAP, 64b is readily acylated by acetic anhydride to form a positively charged planar chiral acylpyridinium species [64b-Ac] (Fig. 43). The latter preferentially reacts with one enantiomer of a racemic alcohol by acyl-transfer thereby regenerating the free catalyst. For this type of reaction, the CsPhs-derivatives 64b/d have been found superior. 

Using water as the solvent enhanced the rate of the hetero-Diels-Alder reaction relative to the dimerization of cyclopentadiene. In addition, the reaction is much faster at a low pH, which implies that the reaction is acid catalyzed. The 5,5-fused system generated has been used in the total synthesis of several bioactive compounds, including the anti-HIV agent (—)-carbovir (Eq. 12.51)121 and the hydroxylactone moiety of mevinic acids (Eq. 12.52).122... 

Domino Michael/aldol addition processes unquestionably represent the largest group of domino transformations. Numerous synthetic applications - for example, in natural product synthesis as well as for the preparation of other bioactive compounds - have been reported. Thus, the procedure is rather flexible and allows the use of many different substrates [12]. In this process it is possible, in theory, to establish up to two new C-C-bonds and three new stereogenic centers in a single step. For example, Collin s group developed a three-component approach. 

Recently, the 2-substituted L-glutamate analogue (2R)-a-(hydroxymethyl)gluta-mate (HMG) (2-151) has been reported by the group of Kozikowski to serve as a potential bioactive compound [73]. Since the synthesis of such a small molecule should be rapid and practical in order to produce it on a multi-gram scale, a domino... 

Cooke and coworkers reported on the synthesis of the amino acid N-benzyl-4-acetylproline (2-889) (Scheme 2.198) [453], as this might represent an interesting synthon for the preparation of bioactive compounds. These authors also used a domino iminium ion formation/aza-Cope/Mannich protocol. Thus, treatment of the secondary amine 2-885 with glyoxylic acid (2-888) primarily provided the corresponding iminium ion, which led to 2-889 in 64% yield as a mixture of diastereom-ers. 

Quinoline derivatives are of major interest as bioactive compounds. A new method for the synthesis of polycyclic fused quinolines 4-207 was developed by Rossi and coworkers [71], who used the [2+2] cycloaddition of an alkyne 4-204 with enamines 4-205 to give 4-206 (Scheme 4.45). Thereby follows an annulation, with the formation of 4-207a-c. 

The formation of the indole moiety has found immense attention, since it exists in many bioactive compounds such as the indole alkaloids [302]. Whilst the Fischer indole synthesis remains the most important procedure, during the past few years several transition metal-catalyzed syntheses have been developed. Recently, a Cu11-catalyzed cyclization of anilines containing an ortho-alkynyl group was published by Hiroya and coworkers [303], which allows a double cyclization in domino fashion to provide annulated indoles. Thus, reaction of 6/4-92 in the presence of... 

Tietze and coworkers developed two new domino approaches in the field of combinatorial chemistry, which are of interest for the synthesis of bioactive compounds. Combinatorial chemistry can be performed either on solid phase or in solution using parallel synthesis. The former approach has the advantage that purification of the products is simple and an excess of reagents can be used. This is not possible for reactions in solution, but on the other hand all known transformations can be used. The Tietze group has now developed a protocol which combines the... 

Macke recently introduced a monoreactive DOTA prochelator (4,7,10-tricarboxymethyl-tert-butyl ester A, A, A", A "-tetraazacyclododecane-1 -acetate), which was coupled to Tyr3—Lys5 (BOQ-octreotide via solid-phase peptide synthesis. A one-step deprotection reaction generated the bioactive compound DOTATOC in about 65% yield.142 The 90Y and 177Lu DOTATOC complexes have shown promise for the treatment of neuroendocrine tumors in early clinical trials.143,444... 

The BINAP-Ru-catalyzed hydrogenation of difunctional ketones has been applied to the asymmetric synthesis of several bioactive compounds (see Fig. 32.12) [1, 49-51]. Stereocenters derived from the BINAP-Ru are labeled by R or S. 

The optically active propargylic and allylic alcohols thus obtained are important synthetic intermediates in the enantioselective synthesis of insect pheromones, prostaglandins, prostacyclins, and many other bioactive compounds (Scheme 6-26).53... 

Concept Organic synthesis is one of the centers of chemistry its domain is not only the preparation of new materials and bioactive compounds but also the production of goods in industry. Its future lies in the development of new efficient methods which allow the formation of complex molecules in a few steps, starting from simple substrates. This is the strength of domino reactions, combining several... 

A complete review on the synthesis of indolizines has appeared <2000HOU(10)745>. This chapter is an extension of the reviews in CHEC(1984) <1984CHEC-I(4)443> and CHEC-II(1996) <1996CHEC-II(8)237>, mainly focusing on the development of synthetic methods aimed at the synthesis of natural alkaloids and important bioactive compounds containing the indolizidine nucleus. 

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