Synthetic Studies on the Taxane Skeleton:  Construction of Eight-Membered Carbocyclic Rings by the Intramolecular <i>B</i>-Alkyl Suzuki−Miyaura Cross-Coupling Reaction

Kawada, Hatsuo; Iwamoto, Mitsuhiro; Utsugi, Masayuki; Miyano, Masayuki; Nakada, Masahisa

doi:10.1021/ol0481939

Cited by 29 publications

(5 citation statements)

References 39 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…On the other hand, a significant breakthrough was achieved when we explored the use of Pd(PPh 3 ) 4 as a catalyst for the Suzuki cyclization event (Scheme 9). Adapting conditions as described by Nakada and coworkers,42 the ring closure of 39 proceeded with surprising efficiency, and the crude product was treated with aqueous acetic acid to yield the diastereomeric lactols 38 (66% yield) after silica gel chromatographic purification. Subsequent oxidation of 38 under mild conditions produced the trans -fused cyclononene lactone 43 .…”

Section: Resultsmentioning

confidence: 99%

Studies for the Synthesis of Xenicane Diterpenes. A Stereocontrolled Total Synthesis of 4-Hydroxydictyolactone

2009

View full text Add to dashboard Cite

The stereocontrolled total synthesis of 4-hydroxydictyolactone (4), a member of the xenicane diterpene family of natural products, is described. These studies feature the development of the B-alkyl Suzuki cross-coupling reaction for direct access to (E)-cyclononenes from acyclic precursors. The Ireland-Claisen rearrangement is effectively utilized to establish the backbone asymmetry of the contiguous C2, C3, C10 stereotriad of 4. The synthesis strategy has devised an intramolecular Nozaki-Hiyama reductive allylation of a formate ester for the stereoselective formation of five-membered lactols 22. In addition, an internally directed SE' propargylation using allenylmagnesium bromide is described to establish the stereochemistry of the C4 alcohol in 27, and the terminal alkyne is subsequently functionalized via a regioselective syn-silylstannylation to yield 30. Finally, the stereocontrolled phenylselenylation of the ester enolate derived from 43 leads to the desired syn-oxidative elimination to yield the natural product 4.

show abstract

Section: Resultsmentioning

confidence: 99%

Studies for the Synthesis of Xenicane Diterpenes. A Stereocontrolled Total Synthesis of 4-Hydroxydictyolactone

2009

View full text Add to dashboard Cite

show abstract

“…Nakada and co-workers − reported a series of synthetic studies toward Taxol since 1998, and culminated in a formal synthesis of Taxol using a convergent strategy in 2015 (Figure ). , Remarkable features of this synthesis were as follows: (i) a 1,2-addition to connect A and C rings at the C1–C2 site; (ii) a Pd-catalyzed alkenylation to install the B ring by C10–C11 bond formation; and (iii) the oxetane D ring was constructed by a well-established S N 2 cyclization.…”

Section: Synthesis Based On Forming the C10–c11 Bondmentioning

confidence: 99%

Strategies and Lessons Learned from Total Synthesis of Taxol

et al. 2023

View full text Add to dashboard Cite

Taxol (paclitaxel), the most well-known taxane diterpenoid, is the best-selling natural-source anticancer drug ever produced and one of the most common prescriptions in the treatment of breast, lung, and ovarian cancers, saving countless lives around the world. Structurally, Taxol possesses a highly oxygenated [6−8−6−4] core bearing 11 stereocenters, seven of which are contiguous chiral centers. Moreover, the extremely strained bicyclo[5.3.1] undecane ring system with a bridgehead double bond is a unique structural feature. All these features make Taxol a highly challenging synthetic target. Tremendous synthetic efforts from more than 60 research groups around the world have already culminated in ten total syntheses and three formal syntheses, as well as more than 60 synthetic model studies of Taxol. This review is intended to provide a long-overdue appraisal of the great achievements in the total syntheses of Taxol reported in the last few decades. In doing so, we summarize the development of synthesis toward Taxol from 1994 to 2022, including the evolution of synthetic strategy for accessing this complex molecular scaffold and key lessons learned from such endeavors. Finally, we briefly discuss the future of the research in this area.

show abstract

“…Utilizing a Chiral Building Block 15 We planned to carry out the coupling of the A and C ring fragments between the C2 and C3 positions of taxol, so that the coupling has to include stereoselective formation of the C2 and C3 stereogenic centers. Hence, the stereoselective coupling reaction was surveyed with model compounds.…”

Section: Enantioselective Preparation Of the C Ring Fragmentmentioning

confidence: 99%

Formal Total Synthesis of (−)-Taxol

Utsugi¹,

Iwamoto²,

Hirai³

et al. 2017

J. Synth. Org. Chem. Jpn.

Self Cite

View full text Add to dashboard Cite

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.

show abstract

Synthetic Studies on the Taxane Skeleton: Construction of Eight-Membered Carbocyclic Rings by the Intramolecular B-Alkyl Suzuki−Miyaura Cross-Coupling Reaction

Cited by 29 publications

References 39 publications

Studies for the Synthesis of Xenicane Diterpenes. A Stereocontrolled Total Synthesis of 4-Hydroxydictyolactone

Studies for the Synthesis of Xenicane Diterpenes. A Stereocontrolled Total Synthesis of 4-Hydroxydictyolactone

Strategies and Lessons Learned from Total Synthesis of Taxol

Formal Total Synthesis of (−)-Taxol

Contact Info

Product

Resources

About