Synthetic studies on the immunosuppressive agent FK-506: Enantioselective synthesis of a C22C34 fragment

Baker, Robert K.; Rupprecht, Kathleen M.; Armistead, David M.; Boger, Joshua; Frankshun, Robert A.; Hodges, P. J.; Hoogsteen, Karst; Pissano, Judith M.; Witzel, B. E.

doi:10.1016/s0040-4039(97)10532-9

Cited by 9 publications

(2 citation statements)

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“…In all of the above examples the enolate was prepared by “soft enolization” (TiCl 4 , i -Pr 2 EtN) . Related examples where transmetalation of a Li enolate was used to prepare the Ti(IV) enolate involve reactions with enantiopure aldehydes, and the corresponding 1,3- syn -1,1′- syn - 11 adducts were formed with varying selectivity depending on whether the reaction was “matched” (dr 20:1) or “mismatched” (dr 1–9:1). , The diastereoselectivities in Table are consistent with the above literature examples. In contrast to the other enolates studied (Tables –), consistently high selectivity (dr ≥9:1) was observed with the Ti(IV) enolates regardless of the relative configuration or protecting group in the starting ketone.…”

Section: Resultssupporting

confidence: 83%

A Systematic Study of the Effects of Relative Configuration, Protecting Group, and Enolate Type on the Diastereoselectivities of Aldol Reactions of a Chiral Ethyl Ketone with 2-Methylpropanal

et al. 2014

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The diastereoselectivities of aldol reactions of 2-methylpropanal with various enolates of 5-O-methoxymethyl and 5-O-triethylsilyl derivatives of the four racemic diastereomers of 6-(2-ethyl-1,3-dioxolan-2-yl)-5-hydroxy-4-methylheptan-3-one are reported. Reactions of the (E)-enol dicyclohexylborinates, (Z)-enol 9-BBN borinates (i.e., 9-((Z)-enoxy)-9-borabicyclo[3.3.1]nonanes), Li (E)-enolates, Li (Z)-enolates, and Ti(IV) (Z)-enolates were examined. Boron and Li enolates were prepared by standard methods, but Ti(IV) enolates were obtained via transmetalation of the Li (Z)-enolates by reaction with TiCln(Oi-Pr)(4-n) (n = 0-2). Aldol relative topicity (simple diastereoselectivity) was strongly correlated to the enolate geometry: anti aldols from (E)-enolates and syn aldols from (Z)-enolates. However, for each enolate type, the diastereoface selectivities varied widely (by factors of 5-400) with the relative configuration and nature of the C5 protecting group in the 8 starting ketones. Plausible transition state models are postulated to rationalize some of these observations. The relative configurations for the complete set of 16 diastereomeric 2-(2-ethyl-1,3-dioxolan-2-yl)-7-hydroxy-3-(methoxymethoxy)-4,6,8-trimethylnonan-5-one aldol adducts were confirmed by NMR analysis of 12 acetonide derivatives prepared from the corresponding 5,7-syn diols. Examination of the NMR data for the above set of aldol adducts revealed consistent trends that were exploited to assign the relative configurations of 13 diastereomeric 2-(2-ethyl-1,3-dioxolan-2-yl)-7-hydroxy-3-(triethylsilyloxy)-4,6,8-trimethylnonan-5-one aldol adducts.

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Section: Resultssupporting

confidence: 83%

A Systematic Study of the Effects of Relative Configuration, Protecting Group, and Enolate Type on the Diastereoselectivities of Aldol Reactions of a Chiral Ethyl Ketone with 2-Methylpropanal

et al. 2014

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“…For example, ( S )-CHCM has been applied to the synthesis of FK-506, the aglycone of the antitumor drug (+)-phyllanthocin, the sex pheromone components periplanone A and B, the toxin pumiliotoxin C, the repellent SS220, the unnatural amino acid β-homoglutamic acid, carbacyclic-(1 → 3)-glucan mimetics, and the inhibitor of coagulant factor Xa (fXa), which is commercially known as Edoxaban and used for the treatment of cancer-associated venous thromboembolism due to its superior oral adsorption and lower bleeding risk compared to those of other anticoagulants (Scheme A) . ( R )-CHCM has also been applied to the synthesis of the immunosuppressant FK-506 (Tacrulimus), the anti-influenza drug oseltamivir phosphate (Tamiflu), the natural products leustroducsin B and phyllanthocin, potential antibacterials, and E-selectin antagonists …”

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confidence: 99%

Kinetic Resolution of Nearly Symmetric 3-Cyclohexene-1-carboxylate Esters Using a Bacterial Carboxylesterase Identified by Genome Mining

et al. 2021

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A new bacterial carboxylesterase (CarEst3) was identified by genome mining and found to efficiently hydrolyze racemic methyl 3-cyclohexene-1-carboxylate (rac-CHCM) with a nearly symmetric structure for the synthesis of (S)-CHCM. CarEst3 displayed a high substrate tolerance and a stable catalytic performance. The enantioselective hydrolysis of 4.0 M (560 g•L −1 ) rac-CHCM was accomplished, yielding (S)-CHCM with a >99% ee, a substrate to catalyst ratio of 1400 g•g −1 , and a space-time yield of 538 g•L −1 •d −1 .

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side chain nitration

Crosby¹

2020

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Synthetic studies on the immunosuppressive agent FK-506: Enantioselective synthesis of a C22C34 fragment

Cited by 9 publications

References 15 publications

A Systematic Study of the Effects of Relative Configuration, Protecting Group, and Enolate Type on the Diastereoselectivities of Aldol Reactions of a Chiral Ethyl Ketone with 2-Methylpropanal

A Systematic Study of the Effects of Relative Configuration, Protecting Group, and Enolate Type on the Diastereoselectivities of Aldol Reactions of a Chiral Ethyl Ketone with 2-Methylpropanal

Kinetic Resolution of Nearly Symmetric 3-Cyclohexene-1-carboxylate Esters Using a Bacterial Carboxylesterase Identified by Genome Mining

side chain nitration

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