Alkyl derivatives natural products synthesis

The appearance of the 2-(indol-3yl)ethylamine (tryptamine) unit in both tryptophan-derived natural products and in synthetic materials having potential pharmacological activity has generated a great deal of interest in the synthesis of such compounds. Several procedures which involve either direct 3-alkylation or tandem 3-functionalization/modification have been developed. Similarly, methodology applicable to preparation of tryptophan analogues has been widely explored. 

This highly convergent synthesis amply demonstrates the utility of Evans s asymmetric aldol and alkylation methodology for the synthesis of polypropionate-derived natural products. By virtue of the molecular complexity and pronounced lability of cytovaricin, this synthesis ranks among the most outstanding synthetic achievements in the macrolide field. 

Alkyl substituted a-lithiodihydrofurans 599-602 and a-lithiodihydropyrans 603-606 have been used for natural product synthesis. They are prepared by deprotonation of the corresponding DHF or DHP derivatives with f-BuLi in THF at —78 to 0 °C. Lithiated DHP 606 has been prepared by tin-lithium transmetallation starting from the hemiacetal 607, by successive transformation into the sulfone 608907 and the stannane 60 9908 (Scheme 163). 

In a second part, the reactivity of a-phenylselanyl enolates, derived from ketones, esters, lactones and a,/i-unsatm ated carbonyl compounds, is discussed. Alkylation, aldolisation and Michael reactions are considered as the use of selenium-stabilized carbanions in the natural product synthesis. Others a-fimctionalyzed species are also presented. 

The oxabicycles are readily amenable for further conversion to a number of useful compounds that have been previously used for synthesis in racemic form. For example, the 5-methyl derivative 81, which is obtained in greater than 99% de after purification by column chromatography, is readily converted to the P-ketoester 82 in 49% overall yield by catalytic hydrogenation with Wilkinson s catalyst, transesterification with sodium methoxide in methanol, and alkylation with methyl iodide (Scheme 29). Racemic 82 was used by Molander in a recent synthesis of 83, an advanced intermediate for natural product synthesis. ... 

With respect to the application of tartaric acid-derived PTCs [22,23] for natural product synthesis, the work of Shibasaki s group should be highlighted herein. Using his powerful bidentate TaDiAS PTCs, asymmetric phase-transfer-catalyzed alkylations, Michael addition reactions, and Mannich-type reactions have been systematically carried out. 

Propiolaldehyde diethyl acetal has found numerous synthetic applications in the literature which may be briefly summarized. The compound has been utilized in the synthesis of unsaturated and polyunsaturated acetals and aldehydes by alkylation of metal-lated derivatives, " by Cadiot-Chodkiewicz coupling with halo acetylenes, " and by reaction with organocuprates. Syntheses of heterocyclic compounds including pyrazoles, isoxazoles, triazoles, and pyrimidines have employed this three-carbon building block. Propiolaldehyde diethyl acetal has also been put to use in the synthesis of such natural products as polyacetylenes " and steroids. ... 

Negishi E, Tan Z (2005) Diastereoselective, Enantioselective, and Regioselective Carbo-alumination Reactions Catalyzed by Zirconocene Derivatives. 8 139-176 Netherton M, Fu GC (2005)Palladium-catalyzed Cross-Coupling Reactions of Unactivated Alkyl Electrophiles with Organometallic Compounds. 14 85-108 NicolaouKC, KingNP, He Y (1998) Ring-Closing Metathesis in the Synthesis of EpothUones and Polyether Natural Products. 1 73-104 Nishiyama H (2004) Cyclopropanation with Ruthenium Catalysts. 11 81-92 Noels A, Demonceau A, Delaude L (2004) Ruthenium Promoted Catalysed Radical Processes toward Fine Chemistry. 11 155-171... 

The ease of converting a nitro group to a carbonyl or other functional group has significantly increased the synthetic potential of nitroalkane derivatives as reagents for the nucleophilic introduction of functionalized alkyl groups in the synthesis of natural products. 

Synthetic applications of the asymmetric Birch reduction and reduction-alkylation are reported. Synthetically useful chiral Intermediates have been obtained from chiral 2-alkoxy-, 2-alkyl-, 2-aryl- and 2-trialkylsllyl-benzamides I and the pyrrolobenzodlazeplne-5,ll-diones II. The availability of a wide range of substituents on the precursor benzoic acid derivative, the uniformly high degree of dlastereoselection in the chiral enolate alkylation step, and the opportunity for further development of stereogenic centers by way of olefin addition reactions make this method unusually versatile for the asymmetric synthesis of natural products and related materials. 

New methods for the synthesis of 2,4-disubstitued oxazoles are summarized in a recent review. 2-Alkyl-1,3-oxazoles bearing alkyl, aryl, or acyl substitution at C4 are common substructures in natural products. Examples include macrolides such as rhizoxin (4), hennoxazole A (5), and phorboxazole A (6), ° as well as many cyclic peptides that incorporate an oxazole subunit presumably derived from serine. ... 

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