Synthesis of the E‐ and Z‐isomers of the potent mutagen (S)‐fecapentaene‐12 by the Horner‐Wittig reaction

Abstract

is described. The method is based on the chromatographic separation of diastereo:meric adducts, formed as intermediates in the Homer-Wittig reaction of an all-trans undecatetraenal with a chiral phosphine oxide.A synthesis of the Eand 2-isomers of optically pure (S)-fecapentaene-12

On the Stereochemistry of Fecapentaene-12

“…Synthetic fecapentaene-12 has been prepared by several methods. In addition to those already cited, which yield, respectively, mixtures of E and Z isomers at the 5-position [3,4] the 1-position [3,5] (10), it has been prepared as the 1-Z isomer [5] (11) and the all-E isomer [3] (11,12). The availability of the isomers 3, 4, and 5 enables us to draw the following conclusions about the stereochemistry of natural fecapentaene-12.…”

“…From these data it can be seen that natural fecapentaene-12 consists of isomers that co-chromatograph with the all-E and 1-Z isomers £3, 5] and the 5-Z isomer £4], The mixture contains one more isomer with an intermediate retention volume. This new isomer may well be the 3-Z isomer £6], ically derived 1-E and 1-Z isomers 3 and 5 (11) indicates that the natural product contains a small amount (approximately 10%) of a 1-Z isomer, probably 5. Surprisingly, the 1-Z isomer 5 and the 1-E isomer 3 co-chromatographed in all the hplc systems we tested, and so it was not possible to obtain independent evidence for the presence of 5 in the natural product.…”

“…EXPERIMENTAL General experimental procedures.-Synthetic methods and analytical techniques were as described previously (13). Pure 1-E and 1-Zfecapentaene-12 [3 and 5] were prepared as previously described (11), and a mixture of 5-E-and 5-Z-fecapentaene-12 [3, 4} was prepared by the method of Nicolaou etal. (9).…”

Quantitative HPLC Analysis of the Level of Fecapentaenes and Their Precursors in Human Feces by a Chemical Conversion Method

“…In accordance with our previous work on the synthesis of naturally occurring fecapentaenes (19)(20)(21), our approach to the synthesis of homologue 6 (Figure 2) was based on the construction of the enol ether double bond by Horner-Wittig coupling of an appropriate polyunsaturated aldehyde with phosphine oxide 7, containing the glyceryl moiety in a suitably protected form (Scheme 2). The requisite aldehyde 8 [(2£, 4E,6E,8£)-dodecatetraenal] was prepared from (2£,4£)-octadienal (22)(23)(24) by a reaction sequence described by Wollenberg (25).…”

My 60-Year Love Affair with Natural Products

“…In later studies we and others − synthesized fecapentaene-12, and we also prepared compounds 22 – 25 with varying numbers of double bonds. Unsurprisingly, mutagenic activity decreased with decreasing numbers of double bonds, and the tetraene 25 was 20–30-fold less mutagenic than fecapentaene-12 …”