The Experts below are selected from a list of 972 Experts worldwide ranked by ideXlab platform
Gunter Helmchen - One of the best experts on this subject based on the ideXlab platform.
-
enantioselective total synthesis of alpha kainic acid
Organic Letters, 2010Co-Authors: Andreas Farwick, Gunter HelmchenAbstract:An enantioselective total synthesis of (-)-alpha-kainic acid is described. Key steps are an Ir-catalyzed allylic amination with a propargylic amine to provide an enyne and a diastereoselective intramolecular Pauson-Khand reaction. Subsequent steps involve a Baeyer-Villiger reaction, reduction of the resulting lactone, and direct Jones Oxidation of a silyl ether.
Peter A. Crooks - One of the best experts on this subject based on the ideXlab platform.
-
asymmetric synthesis of s and r norketamine via sharpless asymmetric dihydroxylation ritter amination sequence
Tetrahedron Letters, 2015Co-Authors: Manfred Biermann, Guangrong Zheng, Marhaba Hojahmat, Nick V. Moskalev, Peter A. CrooksAbstract:Abstract Asymmetric synthesis of (S)-norketamine and (R)-norketamine utilizing Sharpless asymmetric dihydroxylation followed by stereo-controlled Ritter amination and Jones Oxidation is reported. This method allowed the preparation of the free base of (S)-norketamine and (R)-norketamine in pure crystalline form for the first time. The absolute configuration of both enantiomers was verified by X-ray structure and optical resolution of racemic norketamine.
Carlos Roberto Oliveira Souto - One of the best experts on this subject based on the ideXlab platform.
-
Sintese total e enantiosseletiva da aglicona do antibiotico (+)-10-desoximetimicina
2017Co-Authors: Carlos Roberto Oliveira SoutoAbstract:Resumo: Este trabalho descreve a síntese total e enantiosseletiva da 10-Desoximetinolídeo, aglicona do antibiótico 10-Desoximetimicina, um macrolídeo poli oxigenado de 12 membros, através da preparação de dois fragmentos principais os quais foram esterificados e o éster obtido foi submetido a macrociclização através da reação de Nozaki-Hiyama. Estudos para utilização da olefinação de Horner- Wadsworth-Emmons para a macrociclização também foram realizados. O fragmento C1-C7 (+)-152a, equivalente sintético da lactona de Prelog-Djerassi (112a), foi preparado por uma sequência composta de reação aldólica com enolato de boro e um aldeído b-O-tosilado, seguido da alquilação intramolecular do derivado tosilado (-)-308, (esquema 61). A preparação de um cetofosfonato a partir de (+)-152a através da reação com o ânion de lítio do dietilfosfonato de metila não foi possível embora o tenha sido em estudos com a d-lactona modelo 323 (esquema 66 e 67). O fragmento C8-C13 (+)-346 foi também preparado via reação aldólica enantiosseletiva seguido da homologação do aldeído correspondente ao iodeto vinílico 346 através da reação de Takai (esquema 81). A lactona (+)-152a foi então transformada ao ácido carboxílico (-)-339 numa sequência de redução, proteção das hidroxilas e oxidação (esquema 80). O ácido resultante (-)-339 foi esterificado com o fragmento C8-C13 (+)-346. A desproteção da hidroxila primária do éster (+)- 362 e posterior oxidação forneceu o aldeído 367 que foi submetido ao acoplamento intramolecular através da reação de Nozaki-Hiyama. A macrolactona de 12 membros 381 foi obtida em 74% de rendimento na forma de uma mistura de epímeros em C7. Posterior oxidação do álcool alílico e desproteção da hidroxila secundária em C3 forneceu o macrolídeo (+)-2c (esquema 98), espectroscopicamente idêntico (RMN-H e -C) ao descrito em literatura por Cane e colaboradores para a aglicona da 10-desoximetimicina. A síntese do (+)-10-Desoximetinolídeo 2c foi alcançada em 19 etapas e 9,5% de rendimento total em sua rota mais longa a partir do (S)-3-hidroxi-2-metil propionato de metila.Abstract: This work describes the enantioselective total synthesis of (+)-10-Deoxymethynolide (2c), the aglycon of the 12-membered macrolide antibiotic 10-Deoxymethymycin, through the esterification of the C1-C7 and C8-C13 fragments ((-)-339 and (+)-346, respectively) and macrocyclization of the corresponding vinylic iodide-aldehyde via an intramolecular Nozaki- Hiyama reaction. Studies aiming the use of the Horner- Wadsworth-Emmons reaction to accomplish the macrocyclization were also undertaken. The C1-C7 fragment (+)-152a was prepared by an unprecedented aldol reaction of the boron enolate from (R)-4-benzyl-3-propionyl-2-oxazolidinone and a b-O-tosyl aldehyde, followed by an intramolecular alkylation which afforded (+)-152a a synthetic equivalent of the Prelog-Djerassi lactonic acid (112a) (Scheme 61). Lactone (+)-152a was then transformed to the corresponding carboxilic acid (-)-339, after LiAlH4 reduction, 1,3-diol protection, reductive openning and Jones Oxidation (Scheme 80). The C8-C13 fragment (+)-346 was also assembled by an enantioseletive aldol reaction followed by iodoolefination of the corresponding aldehyde under Takai's conditions (Scheme 81). The carboxylic acid (-)-339 was esterified with vinilic iodide (+)-346 using Yamaguchi protocol. Deprotection of the primary alcohol in (+)-362, followed by Dess-Martin Oxidation afforded vinylic iodide-aldehyde 367 which was submitted to the planned macrocyclization mediated by CrCl2/ NiCl2 to afford the corrresponding 12-membered macrolactone in 74% yield as a 1:1 mixture of epimeric alcohol at C7. Oxidation of the these allylic alcohols and deprotection of the secondary alcohol afforded macrolide (+)-2c (Scheme 98). The convergent total synthesis of the (+)-10-Deoxymethynolide (2c) was therefore accomplished in 19 steps and 9,5% yield considering its longest route, starting from the (S)-3-hydroxy-2-methyl methylpropionate
-
Sintese total e enantiosseletiva da aglicona do antibiotico (+)-10-desoximetimicina
Universidade Estadual de Campinas. Instituto de Química, 1998Co-Authors: Carlos Roberto Oliveira SoutoAbstract:Este trabalho descreve a síntese total e enantiosseletiva da 10-Desoximetinolídeo, aglicona do antibiótico 10-Desoximetimicina, um macrolídeo poli oxigenado de 12 membros, através da preparação de dois fragmentos principais os quais foram esterificados e o éster obtido foi submetido a macrociclização através da reação de Nozaki-Hiyama. Estudos para utilização da olefinação de Horner- Wadsworth-Emmons para a macrociclização também foram realizados. O fragmento C1-C7 (+)-152a, equivalente sintético da lactona de Prelog-Djerassi (112a), foi preparado por uma sequência composta de reação aldólica com enolato de boro e um aldeído b-O-tosilado, seguido da alquilação intramolecular do derivado tosilado (-)-308, (esquema 61). A preparação de um cetofosfonato a partir de (+)-152a através da reação com o ânion de lítio do dietilfosfonato de metila não foi possível embora o tenha sido em estudos com a d-lactona modelo 323 (esquema 66 e 67). O fragmento C8-C13 (+)-346 foi também preparado via reação aldólica enantiosseletiva seguido da homologação do aldeído correspondente ao iodeto vinílico 346 através da reação de Takai (esquema 81). A lactona (+)-152a foi então transformada ao ácido carboxílico (-)-339 numa sequência de redução, proteção das hidroxilas e oxidação (esquema 80). O ácido resultante (-)-339 foi esterificado com o fragmento C8-C13 (+)-346. A desproteção da hidroxila primária do éster (+)- 362 e posterior oxidação forneceu o aldeído 367 que foi submetido ao acoplamento intramolecular através da reação de Nozaki-Hiyama. A macrolactona de 12 membros 381 foi obtida em 74% de rendimento na forma de uma mistura de epímeros em C7. Posterior oxidação do álcool alílico e desproteção da hidroxila secundária em C3 forneceu o macrolídeo (+)-2c (esquema 98), espectroscopicamente idêntico (RMN-H e -C) ao descrito em literatura por Cane e colaboradores para a aglicona da 10-desoximetimicina. A síntese do (+)-10-Desoximetinolídeo 2c foi alcançada em 19 etapas e 9,5% de rendimento total em sua rota mais longa a partir do (S)-3-hidroxi-2-metil propionato de metila.This work describes the enantioselective total synthesis of (+)-10-Deoxymethynolide (2c), the aglycon of the 12-membered macrolide antibiotic 10-Deoxymethymycin, through the esterification of the C1-C7 and C8-C13 fragments ((-)-339 and (+)-346, respectively) and macrocyclization of the corresponding vinylic iodide-aldehyde via an intramolecular Nozaki- Hiyama reaction. Studies aiming the use of the Horner- Wadsworth-Emmons reaction to accomplish the macrocyclization were also undertaken. The C1-C7 fragment (+)-152a was prepared by an unprecedented aldol reaction of the boron enolate from (R)-4-benzyl-3-propionyl-2-oxazolidinone and a b-O-tosyl aldehyde, followed by an intramolecular alkylation which afforded (+)-152a a synthetic equivalent of the Prelog-Djerassi lactonic acid (112a) (Scheme 61). Lactone (+)-152a was then transformed to the corresponding carboxilic acid (-)-339, after LiAlH4 reduction, 1,3-diol protection, reductive openning and Jones Oxidation (Scheme 80). The C8-C13 fragment (+)-346 was also assembled by an enantioseletive aldol reaction followed by iodoolefination of the corresponding aldehyde under Takai's conditions (Scheme 81). The carboxylic acid (-)-339 was esterified with vinilic iodide (+)-346 using Yamaguchi protocol. Deprotection of the primary alcohol in (+)-362, followed by Dess-Martin Oxidation afforded vinylic iodide-aldehyde 367 which was submitted to the planned macrocyclization mediated by CrCl2/ NiCl2 to afford the corrresponding 12-membered macrolactone in 74% yield as a 1:1 mixture of epimeric alcohol at C7. Oxidation of the these allylic alcohols and deprotection of the secondary alcohol afforded macrolide (+)-2c (Scheme 98). The convergent total synthesis of the (+)-10-Deoxymethynolide (2c) was therefore accomplished in 19 steps and 9,5% yield considering its longest route, starting from the (S)-3-hydroxy-2-methyl methylpropionate
Bracca, Andrea Beatriz Juana - One of the best experts on this subject based on the ideXlab platform.
-
Expedient approach to 6-bromo-2-isopropylidenecoumaranone, a potential intermediate for the synthesis of TMC-120B, pseudodeflectusin, and Their congeners
'Wiley', 2016Co-Authors: Pergomet, Jorgelina Leonor, Kaufman, Teodoro Saúl, Bracca, Andrea Beatriz JuanaAbstract:A straightforward approach toward 6-bromo-2-isopropylidenecoumaranone, a potential intermediate toward alkaloid TMC 120-B, pseudodeflectusin, and other natural products, was reported. The synthetic sequence involved the reaction of 3-bromosalicylaldehyde with chloroacetone and cyclization of the resulting ether to a 2-acetylcoumaranol intermediate. This was followed by sequential methyl Grignard addition and Jones’ Oxidation to the corresponding coumaranone, which was dehydrated to the final product with the methanesulfonyl chloride/pyridine reagent. The protection of the coumaranol as the corresponding THP-ether resulted in improved product yields.Fil: Pergomet, Jorgelina Leonor. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Química Rosario (IQUIR-CONICET); Argentina.Fil: Kaufman, Teodoro Saúl. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Química Rosario (IQUIR-CONICET); Argentina.Fil: Bracca, Andrea Beatriz Juana. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Química Rosario (IQUIR-CONICET); Argentina
-
Expedient Approach to 6-Bromo-2-isopropylidenecoumaranone, a Potential Intermediate for the Synthesis of TMC-120B, Pseudodeflectusin, and Their Congeners
'Wiley', 2016Co-Authors: Pergomet, Jorgelina Leonor, Kaufman, Teodoro Saúl, Bracca, Andrea Beatriz JuanaAbstract:A straightforward approach toward 6-bromo-2-isopropylidenecoumaranone, a potential intermediate toward alkaloid TMC 120-B, pseudodeflectusin, and other natural products, was reported. The synthetic sequence involved the reaction of 3-bromosalicylaldehyde with chloroacetone and cyclization of the resulting ether to a 2-acetylcoumaranol intermediate. This was followed by sequential methyl Grignard addition and Jones' Oxidation to the corresponding coumaranone, which was dehydrated to the final product with the methanesulfonyl chloride/pyridine reagent. The protection of the coumaranol as the corresponding THP-ether resulted in improved product yields.Fil: Pergomet, Jorgelina Leonor. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Química Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Química Rosario; ArgentinaFil: Kaufman, Teodoro Saul. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Química Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Química Rosario; ArgentinaFil: Bracca, Andrea Beatriz Juana. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Química Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Química Rosario; Argentin
Frank Surup - One of the best experts on this subject based on the ideXlab platform.
-
Viriditins from Byssochlamys spectabilis, their stereochemistry and biosynthesis
Tetrahedron Letters, 2020Co-Authors: Sebastiàn Lòpez-fernàndez, Andrea Campisano, Barbara Joan Schulz, Michael Steinert, Marc Stadler, Frank SurupAbstract:Abstract Byssochlamys spectabilis (anamorph Paecilomyces variotii) strain 10536 was isolated as an endophyte from grapevine and investigated for its secondary metabolite production. Cultures of B. spectabilis yielded the known compound viriditin A (1) and its new derivative viriditin B (2), which showed pronounced cis–trans-amide isomerism. The previously unknown absolute configuration of C–2 and C–13 in 1 were assigned by Mosher’s method. Marfey’s method confirmed 2S stereochemistry after Jones Oxidation and hydrolysis. A series of feeding experiments with [1-13C], [2-13C] and [1, 2-13C2]-acetate as well as [methyl-13C]-methionine indicated a polyketide biosynthetic pathway. Compound 1 showed weak cytotoxicity against the cell line KB3.1 with an IC50 = 30 µg/ml.
