Total Synthesis of (−)- and <i>ent</i>-(+)-Vindoline and Related Alkaloids

Ishikawa, Hayato; Elliott, George C.; Velcicky, Juraj; Choi, Younggi; Boger, Dale L.

doi:10.1021/ja061256t

Cited by 174 publications

(113 citation statements)

References 79 publications

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“…Acidic elimination conditions were counterindicated by the acid-labile protecting groups, which is the reason why we screened elimination reactions under neutral conditions. The Burgess reagent [31] delivered only the respective methylcarboxysulfamate [32] by an addition reaction, while thiocarbonyldiimidazole (Im 2 CS) induced a quantitative elimination. Key to the success of this reaction was the use of a stoichiometric amine base [DMAP = 4-(N,N-dimethylamino)pyridine] to aid proton removal at 40 8C in the absence of solvent.…”

Section: Preparation Of Key Intermediate 5 and Photocycloaddition Expmentioning

confidence: 99%

Total Synthesis of Punctaporonin C by a Regio‐ and Stereoselective [2+2]‐Photocycloaddition

Fleck

Bach

2010

Chemistry A European J

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The unique sesquiterpene punctaporonin C was synthesized starting from commercially available 7-tert-butoxynorbornadiene in a linear sequence of 29 steps and with an overall yield of 0.65%. Key step of the synthesis was an intramolecular [2+2]-photocycloaddition, in which the two vinylic double bonds in a 1,3-divinyl-2-cyclopentyl tetronate were differentiated by reaction with the photoexcited tetronate. The reaction gave regio- and diastereoselective access to the tricyclic core skeleton of punctaporonin C in 63% yield. Additional studies related to the tetronate [2+2]-photocycloaddition revealed that even diastereotopic vinylic double bonds in a 1,3-divinyl-2-cyclopentyl tetronate can be differentiated (d.r. up to 78:22). In the further course of the total synthesis the complete tetracyclic oxatetracyclo[6.3.2.0(1, 4).0(5, 12)]tridecane skeleton of punctaporonin C was established by an intramolecular aldol reaction, closing a seven-membered oxepane ring. The nucleophilic methyl ketone employed in this step was generated by Wacker oxidation of the vinylic double bond, which was not involved in the [2+2]-photocycloaddition. Several reactions employed in the synthetic sequence required adaptation to the rigid skeleton of punctaporonin C, for example, the reduction of a mesylate, the alkylation of a cyclobutane carboxylate, or the methyl addition to a prostereogenic carbonyl group.

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Section: Preparation Of Key Intermediate 5 and Photocycloaddition Expmentioning

confidence: 99%

Total Synthesis of Punctaporonin C by a Regio‐ and Stereoselective [2+2]‐Photocycloaddition

Fleck

Bach

2010

Chemistry A European J

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“…Motivated by their bioactivities and attractive polycyclic structures, enormous synthetic studies on this class of compounds have been carried out. [3][4][5][6][7][8][9] Since the bond formation between the indole and the terpenoid moiety had been well resolved, much effort has been made to enhance the stereoselective construction of the quaternary carbon. Among these studies, strategies based on chiral auxiliary are dominant, and catalytic enantioselective method remains as a challenging task.…”

mentioning

confidence: 99%

Toward General Access to the <i>Aspidosperma</i>-Type Terpenoid Indole Alkaloids: Synthesis of the Key 3,3-Disubstituted Piperidones through Enantioselective Intramolecular Heck-Type Reaction of Chloroformamides

2008

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An enantioselective intramolecular Heck-type reaction of chloroformamides has been developed for the synthesis of 3,3-disubstituted piperidones. The desired piperidone was formed in the presence of a palladium catalyst, an optically active phosphoramidite ligand, K 3 PO 4 and Ag 3 PO 4 . The obtained piperidone was converted to epieburnamonine.Key words enantioselective reaction; total synthesis; terpenoid indole alkaloid Chem. Pharm. Bull. 56(11) 1567-1574 (2008) © 2008 Pharmaceutical Society of Japan * To whom correspondence should be addressed. e-mail: takemoto@pharm.kyoto-u.ac.jp under normal conditions (entries 1-3). However, lactam 9 was isolated in 60% yield when Ag 3 PO 4 was added to the reaction (entry 4). The combination of Pd 2 (dba) 3 and BINAP was also able to promote the cyclization in the presence of Ag 3 PO 4 (entry 5). Nolan's NHC catalyst was not effective (entry 6).With these results in hand, syntheses of each cis-trans isomer of alkenyl chloroformamide 2 were performed. Alkene (E)-4 was synthesized through hydroalumination as a key step (Fig. 5). 4-Pentyn-1-ol (10) was transformed into alcohol 11 through oxidation, acetalization, and hydroxymethylation using benzotriazolylmethanol (BtCH 2 OH). 22) Alcohol 11 was then subjected to the hydroalumination-iodination sequence 23,24) to give (Z)-iodo alkene 12, whose configuration was confirmed by NOE experiment. Ethylation by Suzuki coupling, followed by benzylation gave the desired alkene (E)-4.Change of the starting material afforded the alternative stereoisomer (Fig. 6). (Z)-Iodoalkene 14 was synthesized from 2-pentyn-1-ol (13) through hydroalumination and iodination. Since benzylation of the hydroxy group under either basic or acidic conditions competed with decomposition of the starting material, protection by THP group was carried out. The resultant THP ether 15 underwent Negishi coupling with 3,3-(dimethoxy)propylzinc chloride 16. 25) Selective hydrolysis of the THP ether and benzylation afforded the desired alkene (Z)-4.Alkenyl acetals (E)-4 and (Z)-4 were coupled with tryptamine 3 26) through hydrolysis and reductive amination to give amines (E)-17 and (Z)-17, respectively (Fig. 7). These compounds were converted to the corresponding chloroformamides (E)-2 and (Z)-2 by treating with triphosgene and Et 3 N.Before the enantioselective Heck-type reaction, a racemic reaction was attempted to find out a suitable palladium source ( Table 2). The cyclized product 1 was isolated after hydrolysis of the resultant enol ether. At the early stage, poor reproducibility was a serious problem. After several attempts, it was found that the activity of the catalyst is highly associated with the conditions used to mix palladium sources and ligands prior to the addition of chloroformamide 2. When [Pd(h 3 -C 3 H 5 )Cl] 2 was premixed with (p-tol) 3 P at 30°C for 30 min, the disappearance of 2 was slow and the yield was 30% after 24 h (entry 1). In contrast, the starting material disappeared in 3 h and yield reached 49% when premixing was performed at 40°C...

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“…[50][51][52][53][54][55] This unique domino cascade was used to assemble the fully functionalized pentacyclic ring system of vindoline 118 in a single step that forms four C-C bonds and three rings while introducing all the requisite functionality and setting all six stereocenters within the central ring including three contiguous and four total quaternary centers (Scheme 23). The reaction leading to 117 is initiated by an intramolecular inverse electron demand Diels-Alder cycloaddition of the 1,3,4-oxadiazole 114 with the tethered enol ether.…”

Section: (-)-Vindolinementioning

confidence: 99%

Use of nitrogen and oxygen dipole ylides for alkaloid synthesis

Padwa¹

2018

Arkivoc

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As highlighted in this mini review, a growing area of interest in organic synthesis involves the use of substituted azomethine and carbonyl ylides as 1,3-dipoles for the preparation of alkaloidal natural products. Cascade reactions proceeding by an intramolecular 1,3-dipolar cycloaddition of nitrogen and oxygen dipole ylides are of particular interest to the synthetic organic community because of the increase in molecular complexity involved and the high isolated yields.

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Total Synthesis of (−)- and ent-(+)-Vindoline and Related Alkaloids

Cited by 174 publications

References 79 publications

Total Synthesis of Punctaporonin C by a Regio‐ and Stereoselective [2+2]‐Photocycloaddition

Total Synthesis of Punctaporonin C by a Regio‐ and Stereoselective [2+2]‐Photocycloaddition

Toward General Access to the <i>Aspidosperma</i>-Type Terpenoid Indole Alkaloids: Synthesis of the Key 3,3-Disubstituted Piperidones through Enantioselective Intramolecular Heck-Type Reaction of Chloroformamides

Use of nitrogen and oxygen dipole ylides for alkaloid synthesis

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