Conformer-Specific Photoconversion of 25-Hydroxytachysterol to 25-Hydroxyprevitamin D₃:  Role in the Production of Vitamin Ds

Abstract

The photochemical goal in the production of vitamin Ds (Vit Ds) is to maximize the conversion of the provitamins (Pros) to the previtamins (Pres) while minimizing stoichiometric losses to undesirable over-irradiation products. The last step in the syntheses, the [1,7]-sigmatropic rearrangement of the Pres to the Vits, is thermally induced. The competition between cis-trans photoisomerization and photocyclization of the Pres is known to be highly excitation-wavelength specific. It inspired Havinga's nonequilibration of excited rotamers (NEER) principle and more recent alternative explanations. In contrast, the photochemistry of tachysterol has been reported to be relatively unexceptional with Tachy --> Pre quantum yields in the 0.10-0.13 range, independent of lambdaexc. Examination of the spectrum of the 25-hydroxy derivative of tachysterol (HOTachy) reveals vibronic structure between 295 and 260 nm and a broad structureless shoulder between 330 and 295 nm. These features are consistent with absorption by at least two Tachy conformers. We show that these conformers differ dramatically in their trans-to-cis photoisomerization efficiency. The Tachy --> Pre quantum yield at 313 nm (0.42) in degassed methanol solution is substantially higher than at 254 nm (0.12). On the basis of recent theoretical predictions, it is likely that 313 nm selectively excites the cEc HOTachy conformer which gives photoisomerization much more efficiently than do the other expected conformers (cEt, most abundant, and tEt). Efficient conversion of HOPro D3 to HOPre D3 is accomplished by a two-stage 254/313-nm irradiation sequence. Use of 313 nm in the second step is preferable to previously proposed much longer wavelengths that were hardly absorbed by HOTachy.

The role of tachysterol in vitamin D photosynthesis – a non-adiabatic molecular dynamics study

“…Our results are somewhat different from the assignment of Saltiel et al, 81 who assigned the shoulder at the onset of the Tachy absorption spectrum to the cEc rotamers. Our calculation, however, shows that the shoulder is mainly caused by the tEc rotamers, but also contains a small contribution of the cEc rotamers.…”

Predistortion amplified in the excited state

“…This excites primarily a tachysterol conformer, which is pretwisted. It has a 3.5 times higher quantum yield for E-Z isomerization than the more stable conformer (0.42 versus 0.12), a surprisingly large difference not interpreted in [99]. Obviously the predistortion principle is again at work: it eliminates a minor excited-state barrier (that can be inferred from the low-temperature photostability [100]), and within the shorter times in the accelerated system a larger fraction of the energy is still in the active coordinates, so that momentum effects can affect the branching ratio at the conical intersection.…”

“…2. Saltiel et al [99] found an example, which improves the photochemical synthesis of previtamin D (Scheme 6) or a hydroxyl derivative of it: the E-isomer of previtamin D, tachysterol, an undesired secondary photoproduct, can be reverted to the Z isomer by irradiation in the long-wavelength wing. This excites primarily a tachysterol conformer, which is pretwisted.…”

Previtamin D:Z–Ephotoisomerizationviaa Hula-twist conical intersection

“…(1) The Saltiel group found an example of conformer control, which is of practical interest for the synthesis of (pre)vitamin D and hydroxyl derivatives, 46 for which the predistortion principle provides a suggestive explanation: 42 Whereas the main Tachy conformer (tEc) has an E-Z isomerization quantum yield of only j EZ = 0.12, irradiation in a long-wavelength shoulder (probably belonging to cEc-Tachy) achieves j EZ = 0.42. 46 Indeed cEc-Tachy is more pretwisted than tEc-Tachy. 9 (2) The conformer ratio of the Tachy product was found in ref.…”