Chemoenzymatic Synthesis of the C3–C11‐Fragment of Borrelidin

Abstract

The ex-chiral pool synthesis of the Theodorakis C3-C11 fragment of borrelidin (1) by a chemoenzymatic approach in nine steps and 12 % overall yield starting from enantiopure methyl-branched preen gland wax esters is described. In the initial reaction, the wax ester was (ω-1)-hydroxylated regioselectively by using a mutant of the cytochrome P450

Regioselective Biocatalytic Hydroxylation of Fatty Acids by Cytochrome P450s

“…BM3 and its A74G/F87V/L188Q triple variant were utilized to hydroxylate several multi-methylated fatty acid derivatives (as well as ketones, alcohols; and esters) with activities up to 1204 turnovers per minute [104]. The technology was applied for the synthesis of the C3-C11 fragment of borrelidin at 13 mM substrate concentration (the corresponding methyl-ester) with 34% (184 mg) isolated product after purification [30].…”

“…Despite these issues, fatty acid hydroxylation with enzymes from the cytochrome P450 family is on a more mature level and closer to synthetic application [30], thus this review provides a comprehensive overview of fatty acid hydroxylation reactions catalyzed by cytochrome P450 enzymes close to preparative applications. Substrate concentrations, stereo-, and the regio-selectivity achieved by wildtype enzymes and variants are summarized and only variants with described sequences and reasonable overexpression level are considered.…”

Selective Catalytic Oxidation of CH Bonds with Molecular Oxygen

“…Ester 40 was converted in 8 steps and 36 % overall yield to the C3‐C11 fragment 49 of angiogenesis inhibitor (−)‐borrelidine 50 via anti ‐selective alkylation of Meyer’s pseudo‐ephedrine auxiliary ( R , R )‐ 47 as the key step (Scheme ) 91. 92 As the conversion of compound 49 to the natural product 50 has been already reported,93 this chemoenzymatic sequence provides a formal total synthesis of (−)‐borrelidine 50 .…”

Characterisation of CYP102A25 from Bacillus marmarensis and CYP102A26 from Pontibacillus halophilus: P450 Homologues of BM3 with Preference towards Hydroxylation of Medium‐Chain Fatty Acids

“…The presence of the non‐ionic surfactants Tween 20 and Triton X‐100 did not improve the conversions; however, the addition of methyl‐β‐cyclodextrin gave increased conversions by both P450s. Cyclodextrins have been used previously to aid solubility of hydrophobic substrates in aqueous solutions, including steroids, terpenes and fatty acids . Here, the addition of 4 % ( w / v ) methyl‐β‐cyclodextrin significantly improved the conversion of myristic acid ( 4 ; at 10 m m substrate loading) from approximately 60 % in aqueous solution to 80 %.…”