2182-14-1Relevant articles and documents
Rapid Access to the Highly Oxygenated Aspidosperma Alkaloids Vindoline, Vindorosine, and Cathovaline
Danieli, Bruno,Lesma, Giordano,Palmisano, Giovanni,Riva, Renata
, p. 909 - 911 (1984)
A highly expedient and efficient synthesis of vindoline (1a) and vindorosine (1b), via the hitherto unknown azadienes (3a,b), is reported.
Total synthesis of (?)-vindoline
Chen, Wen,Tian, Hongchang,Tan, Wenyun,Liu, Xiaotong,Yang, Xiaodong,Zhang, Hongbin
, p. 1751 - 1759 (2019)
In this full paper, a stereocontrolled strategy for the total synthesis of (?)-vindoline is described. This synthetic route features: 1) rapid construction of the stereochemical center at C19 through a highly diastereoselective vinylogous Mannich addition; 2) tandem Heathcock/aza-Prins cyclization to install rings C and E in vindoline; 3) oxidative transformation of β-ketoester to enone; 4) stereoselective inversion of C4 stereochemistry with triphenylphosphine and carbon tetrabromide followed by Br?nsted acid.
Asymmetric Total Syntheses of (-)-Jerantinines A, C, and E, (-)-16-Methoxytabersonine, (-)-Vindoline, and (+)-Vinblastine
Wang, Nengzhong,Liu, Jianrong,Wang, Chen,Bai, Leiyang,Jiang, Xuefeng
, p. 292 - 295 (2018)
A concise and stereocontrolled strategy for the syntheses of oxygenated Aspidosperma and Vinca alkaloids, via a stereoselective intermolecular inverse-electron-demand [4 + 2] cycloaddition, a challenging α,β-unsaturated ketone indolization rearrangement with excellent regio- and stereoselectivity, and an efficient Pd/C-catalyzed one-pot cascade reaction. The strategy has been demonstrated by the efficient asymmetric syntheses of antitumor drug (+)-vinblastine and five other oxygenated Aspidosperma alkaloids.
Asymmetric total synthesis of vindoline
Kato, Daisuke,Sasaki, Yoshikazu,Boger, Dale L.
supporting information; experimental part, p. 3685 - 3687 (2010/05/15)
"Chemical equation presented" A concise asymmetric total synthesis of (-)-vindoline (1) is detailed based on a tandem intramolecular [4+2]/[3+2] cycloaddition cascade of a 1,3,4-oxadiazole inspired by the natural product structure, in which the tether linking the initiating dienophile and oxadiazole bears a chiral substituent that controls the facial selectivity of the initiating Diels-Alder reaction and sets absolute stereochemistry of the remaining six stereocenters in the cascade cycloadduct. This key reaction introduces three rings and four C-C bonds central to the pentacyclic ring system setting all six stereocenters and introducing essentially all the functionality found in the natural product in a single step. Implementation of the approach also required the development of a unique ring expansion reaction to provide a six-membered ring suitably functionalized for introduction of the .(6, 7)-double bond found in the core structure of vindoline and defined our use of a protected hydroxymetyl group as the substituent used to control the stereochemical course of the cycloaddition cascade.
Asymmetric total synthesis of vindorosine, vindoline, and key vinblastine analogues
Sasaki, Yoshikazu,Kato, Daisuke,Boger, Dale L.
supporting information; experimental part, p. 13533 - 13544 (2010/12/19)
Concise asymmetric total syntheses of vindoline (1) and vindorosine (2) are detailed based on a unique intramolecular [4 + 2]/[3 + 2] cycloaddition cascade of 1,3,4-oxadiazoles inspired by the natural product structures. A chiral substituent on the tether linking the dienophile and oxadiazole was used to control the facial selectivity of the initiating Diels-Alder reaction and set the absolute stereochemistry of the remaining six stereocenters in the cascade cycloadduct. This key reaction introduced three rings and four C-C bonds central to the pentacyclic ring system setting all six stereocenters and introducing essentially all the functionality found in the natural products in a single step. Implementation of the approach for the synthesis of 1 and 2 required the development of a ring expansion reaction to provide a 6-membered ring suitably functionalized for introduction of the Δ6,7-double bond found in the core structure of the natural products. Two unique approaches were developed that defined our use of a protected hydroxymethyl group as the substituent that controls the stereochemical course of the cycloaddition cascade. In the course of these studies, several analogues of vindoline were prepared containing deep-seated structural changes presently accessible only by total synthesis. These analogues, bearing key modifications at C6-C8, were incorporated into vinblastine analogues and used to probe the unusual importance (100-fold) and define the potential role of the vinblastine Δ6,7-double bond.
Total synthesis of (-)- and ent-(+)-vindoline and related alkaloids
Ishikawa, Hayato,Elliott, Gregory I.,Velcicky, Juraj,Choi, Younggi,Boger, Dale L.
, p. 10596 - 10612 (2007/10/03)
A concise 11-step total synthesis of (-)- and ent-(+)-vindoline (3) is detailed based on a unique tandem intramolecular [4 + 2]/[3 + 2] cycloaddition cascade of a 1,3,4-oxadiazole inspired by the natural product structure, in which three rings and four C-C bonds are formed central to the characteristic pentacyclic ring system setting all six stereocenters and introducing essentially all the functionality found in the natural product in a single step. As key elements of the scope and stereochemical features of the reaction were defined, a series of related natural products of increasing complexity were prepared by total synthesis including both enantiomers of minovine (4), 4-desacetoxy-6,7-dihydrovindorosine (5), 4-desacetoxyvindorosine (6), and vindorosine (7) as well as /V-methylaspidospermidine (11). Subsequent extensions of the approach provided both enantiomers of 6,7-dihydrovindoline (8), 4-desacetoxyvindoline (9), and 4-desacetoxy-6,7-dihydrovindoline (10).
Total synthesis of (-)- and ent-(+)-vindoline
Choi, Younggi,Ishikawa, Hayato,Velcicky, Juraj,Elliott, Gregory I.,Miller, Michael M.,Boger, Dale L.
, p. 4539 - 4542 (2007/10/03)
(Chemical Equation Presented) Two exceptionally concise total syntheses of (-)- and ent-(+)-vindoline are detailed enlisting a diastereoselective tandem [4 + 2]/[3 + 2] cycloaddition of a 1,3,4-oxadiazole. The unique reaction cascade assembles the fully functionalized pentacyclic ring system of vindoline in a single step that forms four C-C bonds and three rings while introducing all requisite functionality and setting all six stereocenters within the central ring including three contiguous and four total quaternary centers.
An efficient total synthesis of (-)-vindoline
Kobayashi, Satoshi,Ueda, Toshihiro,Fukuyama, Tohru
, p. 883 - 886 (2007/10/03)
A highly efficient total synthesis of the title compound is described. Our synthesis features a highly efficient preparation of the key intermediate 11 using our novel indole synthesis methodology. A novel amine protecting protocol by means of 2,4-dinitrobenzenesulfonamides has been developed to ensure the formation of the elusive secodine-type intermediate 15 under very mild conditions.
Novel alkaloids
-
, (2008/06/13)
Cycloalkyl and aromatic vinblastine and vincristine derivatives useful as anti-tumor agents.
Biomimetic Alkaloid Syntheses. 15. Enantioselective Syntheses with Epichlorohydrin: Total Syntheses of (+)-, (-)-, and (+/-)-Vindoline and a Synthesis of (-)-Vindorosine
Kuehne, Martin E.,Podhorez, David E.,Mulamba, Tshilundu,Bornmann, William G.
, p. 347 - 353 (2007/10/02)
Total syntheses of vindoline (1) in racemic as well as in each enantiomeric form and of (-)-vindorosine (2) are described.They were achieved by generation and diastereoselective cyclizations of 14-hydroxysecodine intermediates 6 and 7.The subsequent oxidative elaboration of ring E was also studied with 3-oxotabersonine (24), 3-oxovincadifformine (26), and 14β-hydroxyvincadifformine (15).Na-Methyltabersonine (22) was oxidized to a ring-D-contracted α-keto lactam, 23.
