Formal Total Synthesis of (−)‐Taxol through Pd‐Catalyzed Eight‐Membered Carbocyclic Ring Formation

Hirai, Sho; Utsugi, Masayuki; Iwamoto, Mitsuhiro; Nakada, Masahisa

doi:10.1002/chem.201404295

Cited by 69 publications

(52 citation statements)

References 51 publications

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“…The synthetic utility of this methodology was demonstrated by a four-step one-pot synthesis and a successful recycling of the reaction medium [127]. B-alkyl SMC, in particular, was likewise applied in the synthesis of beneficial products [130][131][132]. Two examples are shown in Scheme 16: Cytochalasin Z 8 and Ieodomycin D, which belong to the family of secondary fungal metabolite with a wide range of biological activities that target cytoskeletal processes [133][134][135].…”

Section: B-alkyl Smcs Using Bbn Variants (9-meo-9-bbn and Obbd Derivamentioning

confidence: 99%

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Recent Advances in Metal-Catalyzed Alkyl–Boron (C(sp3)–C(sp2)) Suzuki-Miyaura Cross-Couplings

El‐Maiss

Dine

et al. 2020

Catalysts

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Boron chemistry has evolved to become one of the most diverse and applied fields in organic synthesis and catalysis. Various valuable reactions such as hydroborylations and Suzuki–Miyaura cross-couplings (SMCs) are now considered as indispensable methods in the synthetic toolbox of researchers in academia and industry. The development of novel sterically- and electronically-demanding C(sp3)–Boron reagents and their subsequent metal-catalyzed cross-couplings attracts strong attention and serves in turn to expedite the wheel of innovative applications of otherwise challenging organic adducts in different fields. This review describes the significant progress in the utilization of classical and novel C(sp3)–B reagents (9-BBN and 9-MeO-9-BBN, trifluoroboronates, alkylboranes, alkylboronic acids, MIDA, etc.) as coupling partners in challenging metal-catalyzed C(sp3)–C(sp2) cross-coupling reactions, such as B-alkyl SMCs after 2001.

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Section: B-alkyl Smcs Using Bbn Variants (9-meo-9-bbn and Obbd Derivamentioning

confidence: 99%

“…B-alkyl SMC, in particular, was likewise applied in the synthesis of beneficial products [130][131][132]. Two examples are shown in Scheme 16: Cytochalasin Z8 and Ieodomycin D, which belong to the family of secondary fungal metabolite with a wide range of biological activities that target…”

Section: Selected Examples Of Applications Of Smcs and B-alkyl Smc Inmentioning

confidence: 99%

Recent Advances in Metal-Catalyzed Alkyl–Boron (C(sp3)–C(sp2)) Suzuki-Miyaura Cross-Couplings

El‐Maiss

Dine

et al. 2020

Catalysts

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“…Palladium Catalyzed Alkenylation of a Methyl Ketone 13 We applied the palladium catalyzed alkenylation of a methyl ketone to the total synthesis of taxol. Two fragments, the A ring fragment 14 I and the C ring fragment 66, were assembled to afford 67 I as a single isomer via a halogen lithium exchange reaction (Scheme 21).…”

Section: Formal Total Synthesis Of ( ) Taxol Viamentioning

confidence: 99%

Formal Total Synthesis of (−)-Taxol

Utsugi¹,

Iwamoto²,

Hirai³

et al. 2017

J. Synth. Org. Chem. Jpn.

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Formal total synthesis of ( ) taxol is described herein. This convergent synthesis was accomplished by utilizing two chiral fragments, both of which were prepared via asymmetric catalysis. A palladium catalyzed reaction was found to afford the eight membered ring effectively, i.e., a B alkyl Suzuki Miyaura coupling reaction and an intramolecular alkenylation of a methyl ketone successfully constructed the B ring of taxol in excellent yield. During the preparation of a substrate for the palladium catalyzed reaction, a unique rearrangement of the epoxy benzyl ether, via a 1,5 hydride shift that generates the C3 stereogenic center and subsequently forms the C1 C2 benzylidene moiety, was observed. Strenuous efforts were required for transformations after the construction of the taxane scaffold to achieve the formal total synthesis of taxol because very few approaches are available for the synthesis of the target compound.

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“…The spectacular clinical success of taxanes combined with their stunning complexity has motivated and inspired scores of chemists over the past several decades. [1][2][3] Indeed, Taxol (1, Figure 1) can be treated as ab arometer to measure progress and advances in the science of chemical synthesis.This iconic natural product has been prepared on ten separate occasions (seven total syntheses [4][5][6][7][8][9][10][11][12] and three formal syntheses [13][14][15][16] ), thus elegantly demonstrating the feasibility of its reconstitution by purely chemical means.Notwithstanding the beauty of these landmark accomplishments,t hey are eight to nine orders of magnitude less efficient than biological production. To be sure,m ere milligrams were produced all together by total synthesis,w hereas metric tons of Taxol are accessed every year through ap lant cell culture process developed by Bristol-Myers Squibb and Phyton Biotech, Inc.…”

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confidence: 99%

Short, Enantioselective Total Synthesis of Highly Oxidized Taxanes

et al. 2016

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In the realm of natural product chemistry, few isolates have risen to the level of fame justifiably accorded to Taxol (1) and its chemical siblings. This report describes the most concise route to date for accessing the highly oxidized members of this family. As representative members of taxanes containing five oxygen atoms, decinnamoyltaxinine E (2) and taxabaccatin III (3), have succumbed to enantioselective total synthesis for the first time in only 18 steps from a simple olefin starting material. The strategy holistically mimics natures approach (two-phase synthesis) and features a carefully choreographed sequence of stereoselective oxidations and a remarkable redox-isomerization to set the key trans-diol present in 2 and 3. This work lays the critical groundwork necessary to access even higher oxidized taxanes such as 1 in a more practical fashion, thus empowering a medicinal chemistry campaign that is not wedded to semi-synthesis.[ + ] These authors contributed equally.Supporting information and the ORCID identification number(s) for the author(s) of this article can be found under http://dx.

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Formal Total Synthesis of (−)‐Taxol through Pd‐Catalyzed Eight‐Membered Carbocyclic Ring Formation

Cited by 69 publications

References 51 publications

Recent Advances in Metal-Catalyzed Alkyl–Boron (C(sp3)–C(sp2)) Suzuki-Miyaura Cross-Couplings

Recent Advances in Metal-Catalyzed Alkyl–Boron (C(sp3)–C(sp2)) Suzuki-Miyaura Cross-Couplings

Formal Total Synthesis of (−)-Taxol

Short, Enantioselective Total Synthesis of Highly Oxidized Taxanes

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