Studies towards asymmetric synthesis of 4(S)-11-dihydroxydocosahexaenoic acid (diHDHA) featuring cross-coupling of chiral stannane under mild conditions

Abstract

An efficient and asymmetric synthetic approach towards one of the biologically interesting 4(S)-11-diHDHA derivatives was developed. This process mainly relied on two reactions, one is the copper-catalyzed mild cross-coupling that allows for the efficient construction of a chiral α-alkynyl α-hydroxy motif and another is the synthesis of chiral α-hydroxy α-stannanes that has previously been developed by our group featuring the asymmetric stannylation using the well-established tributyltin hydride/diethyl zinc system from an aldehyde.

Advances in non‐palladium‐catalysed Stille couplings

“…The E isomer was obtained in excellent yields of up to 94%. A large increment in the ratio of S C H E M E 1 9 Cu(I)-catalysed Stille coupling reactions involved in the synthesis of 4(S)-11-Dihydroxydocosahexaenoic acid [55] S C H E M E 2 0 Scope of nano-copper catalyst in the synthesis of biphenyls [56] the E-adduct has also been noticed in THF media. A possible mechanism is depicted in Scheme 22.…”

“…The well‐studied CuTC‐catalysed cross‐coupling reaction as one of the key stages in the enantioselective synthesis of biologically significant 4( S )‐11 dihydroxydocosahexaenoic acid (diHDHA) has been reported by Wang and Falck. [ 55 ] The construction of the necessary chiral Csp‐Csp 3 ‐bonded motifs of diHDHA was realised by the coupling of chiral α ‐hydroxy stannanes with conjugated bromides under mild cross‐coupling conditions. This Cu‐catalysed Stille coupling is performed twice during the synthesis for the efficient construction of chiral α ‐alkynyl α‐hydroxy motifs (Scheme 19).…”

“…Cu(I)‐catalysed Stille coupling reactions involved in the synthesis of 4( S )‐11‐Dihydroxydocosahexaenoic acid [ 55 ] …”

“Clicking” Gene Therapeutics: A Successful Union of Chemistry and Biomedicine for New Solutions

“…Wang et al used SPAAC to modify DNA with diverse functionalities. 37 SPAAC has advantages of high reaction rate at ultramild conditions when the two molecules to be reacted have no steric hindrance. However, the rate of SPAAC can be lower compared to CuAAC when clicking longer peptides (>20 amino acids) to oligonucleotides.…”

Total Syntheses of Two bis‐Allylic‐Deuterated DHA Analogues

“…We envisaged as ynthesis of aldehyde 3b from compound 3a in five steps as described by Wang et al [33] Thus, the reduction of compound 3a with NaBH 4 afforded homoallylic alcohol 22,w hich was treated with vanadyl acetylacetonate (VO(acac) 2 ) and tBuOOH to give intermediate epoxide alcohol 23.R ingopeningo ft he epoxide was first performed with perchloric acid, which led to an unstabletriol intermediate that was treated with sodium periodate to promote oxidative cleavage. However,d isappointingly,u nder these conditions, compound 3b was isolated in unacceptablep urity for its use in the Wittig reaction.…”