73327-06-7Relevant academic research and scientific papers
Enantiospecific Formation of Trans 1,3-Disubstituted Tetrahydro-β-carbolines by the Pictet-Spengler Reaction and Conversion of Cis Diastereomers into Their Trans Counterparts by Scission of the C-1/N-2 Bond
Cox, Eric D.,Hamaker, Linda K.,Li, Jin,Yu, Peng,Czerwinski, Kevin M.,Deng, Li,Bennett, Dennis W.,Cook, James M.,Watson, William H.,Krawiec, Mariusz
, p. 44 - 61 (2007/10/03)
The factors which effect the stereoselective formation of trans-1-alkyl-2-benzyl-3-(alkoxycarbonyl)-1,2,3,4-tetrahydro-β-carbolines and trans-3-(alkoxycarbonyl)-1-alkyl-2-(diphenylmethyl)-1,2,3,4-tetrahydro-β- carbolines by the Pictet-Spengler cyclization were examined by heating tryptophan derivatives with aldehydes of varied steric bulk under aprotic and acidic conditions, followed by determination of the ratio of cis to trans diastereomers so formed. The presence of a benzyl group at the Nb-nitrogen atom alters the diastereochemical outcome of this condensation to provide 100% trans stereoselectivity when the cyclization is carried out with cyclohexanecarboxaldehyde. Furthermore, when Nb-(diphenylmethyl)tryptophan isopropyl ester was condensed with aldehydes of any size, trans diastereomers are formed with 100% stereoselectively. The trans Nb-substituted diastereomers are thermodynamically more stable than their cis congeners as shown by equilibration experiments in TFA. Conversion of the cis diastereomers into the more stable trans diastereomers is believed to occur under acidic conditions by cleavage of the carbon (C-1)-nitrogen (N-2) bond with complete retention of configuration at the C-3 stereocenter. Evidence from deuterium exchange experiments as well as optical rotations support this model for epimerization. In addition, when cis diastereomer 66a was allowed to stir in CF3COOD, the trans isomer 66b was isolated in 90% yield, while treatment of cis 66a with CF3COOH/NaBH4 provided a mixture of the ring cleaved [scission across C(1)-N(2) bond] product 67 and the trans isomer 66b. Treatment of 66b (control experiment) with NaBH4/CF3COOH under the same conditions returned only starting trans 66b in excellent yield. The Pictet-Spengler reaction of substrates with sufficiently large substituants, followed by treatment with acid, permits the 100% enantiospecific formation of trans-1,3-disubstituted-1,2,3,4-tetrahydro-β-carbolines for alkaloid total synthesis.
Mechanism driven trans stereospecificity in the Pictet-Spengler reaction. Stereospecific formation of trans-1,2,3-trisubstituted-tetrahydro β-carbolines by condensation of N(b)-diphenylmethyl tryptophan isopropyl esters with aldehydes
Czerwinski,Deng,Cook
, p. 4721 - 4724 (2007/10/02)
Stereoelectronic control in the Pictet-Spengler condensation of N(b)-alkylsubstituted tryptophan alkyl esters has been employed to promote 100% stereoselectivity in this process. The reaction of N(b)-diphenylmethyl tryptophan isopropyl ester 8 with acetal
A NEW METHOD FOR THE PREPARATION OF 3,4-DIHYDRO AND 1,2,3,4-TETRAHYDRO-β-CARBOLINES
Nakamura, Tohru,Ishida, Akihiko,Irie, Kunihiko,Oh-ishi, Tokuro
, p. 2859 - 2862 (2007/10/02)
The NaBH4 reduction of 1,3-disubstituted 3,4-dihydro-β-carbolines (2) gave cis (3)- or trans -1,2,3,4-tetrahydro-β-carbolines (4) with satisfactory stereoselectivity.The synthesis of optically active 2 and 3 is also described.KEYWORDS - Nb-thio
Pictet-Spengler Reactions in Aprotic Media
Jawdosiuk, Mikolaj,Cook, James M.
, p. 2699 - 2701 (2007/10/02)
The reaction of tryptophan methyl ester (1) with aldehydes such as benzaldehyde (2a) and cyclohexanecarboxaldehyde (2b) in refluxing benzene provides the corresponding tetrahydro-β-carbolines 5a and 5b, respectively, as earlier reported, in contrast to th
Stereospecific Synthesis of trans-1,3-Disubstituted-1,2,3,4-tetrahydro-β-carbolines
Ungemach, F.,DiPierro, M.,Weber, R.,Cook, J. M.
, p. 164 - 168 (2007/10/02)
The Pictet-Spengler condensation of Nb-benzyltryptophan methyl ester 1a with aldehydes 2a-d has been found to occur in a stereospcific fashion.Stereoelectronic (antiperiplanar) attack of the 2,3-indole double bond on the intermediate benziminiu
