Asymmetric Total Synthesis of TaxolR

Mukaiyama, Teruaki; Shiina, Isamu; Iwadare, Hayato; Saitoh, Masahiro; Nishimura, Toshihiro; Ohkawa, Naoto; Sakoh, Hiroki; Nishimura, Kazunori; Tani, Yu Ichirou; Hasegawa, Masatoshi; Yamada, Kôji; Saitoh, Katsuyuki

doi:10.1002/(sici)1521-3765(19990104)5:1<121::aid-chem121>3.3.co;2-f

Cited by 64 publications

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“…In Mukaiyama's elegant taxol synthesis, a key reaction involves a similar type of β-chelation, specifically the MgBr 2 -mediated reaction of aldehyde 79 with enol silane 80 (Scheme 19). 41 The reaction provides the anti/anti/anti-adduct 81 with excellent 1,3-asymmetric induction.…”

Section: 3-asymmetric Inductionmentioning

confidence: 99%

The Chelation-controlled Mukaiyama Aldol Reaction of Chiral α- and β-Alkoxy Aldehydes

2013

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The concept of treating chiral α- and β-alkoxy aldehydes with bicoordinate Lewis acids such as TiCl₄, SnCl₄, or MgBr₂ followed by the addition of carbon nucleophiles for achieving chelation control with 1,2- and 1,3-asymmetric induction, respectively, was introduced three decades ago and has since evolved into a general method. In the case of enol silanes, the chelation-controlled Mukaiyama aldol reaction is involved, which has been used in recent natural products syntheses

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Section: 3-asymmetric Inductionmentioning

confidence: 99%

The Chelation-controlled Mukaiyama Aldol Reaction of Chiral α- and β-Alkoxy Aldehydes

2013

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“…In the past decade, six groups succeeded in the total synthesis of 1 4) including the enantioselective synthesis, 5) and a number of structure-activity relationships (SAR) of 1 and its modified compounds have been reported by several groups. 6) Our attention has been focused on the establishment of a novel synthetic route to 1, and we found that the reaction of sulfone (4 or 7) with potassium hexamethyldisilazide (KN(SiMe 3 ) 2 ) provided the bicyclo[6.…”

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“…6) Our attention has been focused on the establishment of a novel synthetic route to 1, and we found that the reaction of sulfone (4 or 7) with potassium hexamethyldisilazide (KN(SiMe 3 ) 2 ) provided the bicyclo[6. 4.0]dodecenone (8 or 9) (Chart 1). 7) Although many SAR studies between biological activities and functional groups of taxol have been reported, 6) there is little research describing the influence of the 6-8-6 fused ring skeleton on these biological activities.…”

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“…Expecting that it would be worth biologically evaluating bicyclo[6. 4.0]dodecenone compounds, we investigated their activities on malaria (Plasmodium falciparum) 8) and human KB cells. 9) The former is one of the most serious human malaria parasites in the tropical areas, and the rapid acquisition of resistance by P. falciparum to the drug chloroquine has recently become a significant problem.…”

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Antimalarial and Cytotoxic Activities of Bicyclo[6.4.0]dodecenones.

Fujishima

Takeshita

Toyota

et al. 2001

CHEMICAL & PHARMACEUTICAL BULLETIN

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Since the identification of the structure of taxol (1) (Fig. 1) by Wani and co-workers 1) and the elucidation of its unusual mode of action,2) structural features of the taxane diterpens consisting of the 6-8-6 fused ring system and promising activities against several important human cancers 3) have stimulated the attention of numerous organic and biological chemists. In the past decade, six groups succeeded in the total synthesis of 1 4) including the enantioselective synthesis, 5) and a number of structure-activity relationships (SAR) of 1 and its modified compounds have been reported by several groups. 6)Our attention has been focused on the establishment of a novel synthetic route to 1, and we found that the reaction of sulfone (4 or 7) with potassium hexamethyldisilazide (KN(SiMe 3 ) 2 ) provided the bicyclo[6.4.0]dodecenone (8 or 9) (Chart 1). 7) Although many SAR studies between biological activities and functional groups of taxol have been reported, 6) there is little research describing the influence of the 6-8-6 fused ring skeleton on these biological activities. Expecting that it would be worth biologically evaluating bicyclo[6.4.0]dodecenone compounds, we investigated their activities on malaria (Plasmodium falciparum) 8) and human KB cells.9) The former is one of the most serious human malaria parasites in the tropical areas, and the rapid acquisition of resistance by P. falciparum to the drug chloroquine has recently become a significant problem. In the in vitro assay of malaria, mouse mammary tumor FM3A cells in culture were used as a control for mammalian cell cytotoxicity. We now report interesting biological activities of bicyclo[6.4.0]dodecenone derivatives. Results and DiscussionSyntheses of Substrates Sulfones (4, 7) were prepared through the corresponding intermediates (3, 6) which were derived from a common material, cyclohexadienyl aldehyde (2).7a) The intramolecular Michael reaction of 4 or 7 with KN(SiMe 3 ) 2 in tetrahydrofuran (THF) provided the cis-fused bicyclo[6.4.0]dodecenone compound (8 or 9) in quantitative yield, respectively. 9 was reacted with L-Selectride ® (1 M in THF solution) to produce the allylic alcohol (10) with high diastereoselectivity 7b) (Chart 2). Treatment of enone (8 or 9) with electrophiles, such as tert-butyldimethylsilyl trifluoromethanesulfonate (TBSOTf) or methoxymethyl chloride (MOMCl), under the basic conditions furnished the TBS enolether (11) in 63% yield or the MOM enolether (12) in 59% yield. In the latter reaction, the C-alkylated product (13) was also obtained in 18% yield. In addition, it was found that quenching the cyclization reaction of 4 or 7 with excess amounts of MOMCl afforded the exo-olefinated product (14 or 15) in high yield. 7b) Oxidation of the exo-olefin moiety with hydrogen peroxide (30% aqueous solution) in the mixture of 6 M NaOH aqueous solution and MeOH at room temperature provided the epoxide (16) Aobayama, Japan, Faculty of Pharmaceutical Sciences, Okayama University, Japan, and Department of Experimental Therapeutics, C...

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