Isolation and Characterization of Two Geometric Allene Oxide Isomers Synthesized from 9S-Hydroperoxylinoleic Acid by Cytochrome P450 CYP74C3

Abstract

Background: Allene oxides involved in cyclopentenone biosynthesis are extremely labile and have eluded full stereochemical assignment. Results: We identify a novel Z-allene oxide that unexpectedly rearranges to a cyclopentenone. Conclusion: Other natural allene oxides are assigned the E configuration and can be easily distinguished from the Z-allene oxide by NMR. Significance: Unequivocal determination of the unknown allene oxide configuration is documented and helps elucidate the cyclization chemistry.

A unifying mechanism for the rearrangement of vinyl allene oxide geometric isomers to cyclopentenones

“…The rearrangement of vinyl allene oxides with the S,Z,E-1 configuration would produce the trans-cyclopentenone 3 of 4S,5R absolute configuration following motions with the same handedness as those of S,Z,Z-1. This unifying mechanism is consistent with the following experimental observations related to vinyl allene oxides derived from unsaturated fatty acid hydroperoxides: (1) the cyclopentenone is formed more rapidly from the isolated Z vinyl allene oxide than from the E isomer, as shown; 12 (2) ciscyclopentenones are the primary products (except for systems having the yet undescribed S,Z,E-1 configuration) under conditions that prevent epimerization at C5; 12 (3) the rearrangement of enantiopure vinyl allene oxides of S,Z,Z (like the one from γ-linolenic acid 9-hydroperoxides) 12 and S,Z,E configurations could take place with memory of chirality and afford enantioenriched products; this effect is unlikely for vinyl allene oxides with S,E,E configuration (in the experimental setting, also for those with S,E,Z configuration) due to the small energy difference between the stepwise and concerted options; 3b,c (4) Favorskii-type by-products derived from the cyclopropanone intermediate could be formed; these secondary products have indeed been isolated upon incubation of α-and γ-linolenic acid 13-and 9-hydroperoxides (respectively) with AOSs. 34 …”

“…33 Moreover, Brash and coworkers detected partial chirality transfer (er of 61 : 39 and 53 : 47 in the two measurements; no assignment of absolute configuration was carried out) when the Z vinyl allene oxide from 9S-HPODE was derivatized as methyl ester and allowed to stand in the HPLC solvent. 12 To probe that this mechanism is indeed general, we have computed the mechanistic manifold for the geometric isomers of the reactant at the conjugated double bond, namely S,E,E-1 and S,Z,E-1. Scheme 4 shows a similar scenario comprising concerted and stepwise alternatives for the rearrangement of these geometric isomers.…”

A new class of fatty acid allene oxide formed by the DOX-P450 fusion proteins of human and plant pathogenic fungi, C. immitis and Z. tritici

“…The allene oxides can be transformed enzymatically or nonenzymatically to cyclopentenone fatty acids, e.g., analogs of jasmonic acid and prostaglandin A 2 , respectively (37)(38)(39). The process leading to a cyclopentenone from the 10Z-isomer of the 9S-HPODE-derived allene oxide was recently studied in detail (40,41). This allene oxide undergoes homolytic cleavage with formation of a ketone at C-10, a radical at C-9, and an allyl-like radical at C-11 to C-13.…”

Discovery of a linoleate 9S-dioxygenase and an allene oxide synthase in a fusion protein of Fusarium oxysporum

“…Allene oxides are unstable in aqueous solutions with nonenzymatic hydrolysis to ␣ -and ␥ -ketols as illustrated in Fig. 8B , but allene oxides can be isolated and purifi ed at low temperatures ( 7,44 ).…”