1,4-syn-Asymmetric induction in the titanium-mediated aldol reactions of chiral methyl α-silyloxy ketones

The total synthesis of amphidinolide B1 and the proposed structure of amphidinolide B2 has been accomplished. Key aspects of this work include the development of a practical, non-transition metal mediated method for the construction of the C13-C15 diene, the identification of α-chelation and dipole minimization models for diastereoselective methyl ketone aldol reactions, the discovery of a spontaneous Horner-Wadsworth-Emmons macrocyclization strategy and the development of a novel late stage method for construction of an allylic epoxide moiety. The originally proposed structure for amphidinolide B2 and diastereomers thereof display potent anti-tumor activities with IC50 values ranging from 3.3 nM to 94.5 nM against human solid and blood tumor cells. Of the different stereoisomers, the proposed structure of amphidinolide B2 is over 12-fold more potent than the C8,9-epimer and C18-epimer in human DU145 prostate cancer cells. These data suggest that the epoxide stereochemistry is a significant factor for anticancer activity.

show abstract

“…Other laboratories have subsequently explored this transformation with varying degrees of stereocontrol. 32 …”

Section: Resultsmentioning

confidence: 99%

Amphidinolide B: Total Synthesis, Structural Investigation, and Biological Evaluation

et al. 2013

View full text Add to dashboard Cite

show abstract

“…Eventually, we centered our attention on the α‐ tert ‐butyldimethylsilyloxy methyl ketone 3 17e. Since the stereoselective acetate aldol reaction still represents a challenge,23 we considered that the application of the combined aldol and reduction reactions on that chiral methyl ketone would definitely prove the synthetic efficiency of the abovementioned transformation.…”

Section: Resultsmentioning

confidence: 99%

Highly Stereoselective Synthesis of syn‐1,3‐Diols through a Sequential Titanium‐Mediated Aldol Reaction and LiBH₄ Reduction

et al. 2010

Self Cite

View full text Add to dashboard Cite

show abstract

“…These results were optimized for α‐ tert ‐butyldimethylsilyloxy methyl ketones, which preferentially afforded 1,4‐ syn aldols 52. Similarly, titanium(IV) enolates of chiral β‐benzyloxy methyl ketones 38 reacted with numerous saturated and unsaturated aldehydes, leading predominantly to 1,4‐ syn enantiomers 40 53a.…”

Section: Titanium(iv) Enolates In Aldol Reactionsmentioning

confidence: 99%

Titanium Enolate Chemistry at the Beginning of the 21st Century

2016

View full text Add to dashboard Cite

show abstract

1,4-syn-Asymmetric induction in the titanium-mediated aldol reactions of chiral methyl α-silyloxy ketones

Cited by 14 publications

References 26 publications

Amphidinolide B: Total Synthesis, Structural Investigation, and Biological Evaluation

Amphidinolide B: Total Synthesis, Structural Investigation, and Biological Evaluation

Highly Stereoselective Synthesis of syn‐1,3‐Diols through a Sequential Titanium‐Mediated Aldol Reaction and LiBH₄ Reduction

Titanium Enolate Chemistry at the Beginning of the 21st Century

Contact Info

Product

Resources

About

1,4-syn-Asymmetric induction in the titanium-mediated aldol reactions of chiral methyl α-silyloxy ketones

Cited by 14 publications

References 26 publications

Amphidinolide B: Total Synthesis, Structural Investigation, and Biological Evaluation

Amphidinolide B: Total Synthesis, Structural Investigation, and Biological Evaluation

Highly Stereoselective Synthesis of syn‐1,3‐Diols through a Sequential Titanium‐Mediated Aldol Reaction and LiBH4 Reduction

Titanium Enolate Chemistry at the Beginning of the 21st Century

Contact Info

Product

Resources

About

Highly Stereoselective Synthesis of syn‐1,3‐Diols through a Sequential Titanium‐Mediated Aldol Reaction and LiBH₄ Reduction