Calculated heats of formation of sterol diene isomers compared with synthetic yields of isomerisation reactions of Delta(5,7) sterols

Heats of formation of five series of diene sterol isomers were calculated a nd compared with synthetic yields of acid-catalysed isomerisation reactions starting from Delta(5,7) isomers. Calculations were based on molecular mec hanics, using the MM3 program package. For each of the five Delta(5,7) star ting compounds, three possible reaction paths were considered, in which hea ts of formation were calculated for theoretically possible intermediate dou ble bond isomers. Similar results are found for all five series. The starti ng compounds are found to have the unfavourable heats of formation compared to all other isomers considered within one series. In general, isomerisati on reactions of diene sterols ultimately yield spiro compounds when allowed to proceed for a sufficient amount of time. These compounds are found to h ave the lowest heats of formation in each series. However, they were not fo rmed in the reactions considered in this paper, because the reactions were stopped after the desired isomer was formed in excess, before the spiro com pounds could occur. Most compounds identified as products in the syntheses have a favourable heat of formation compared to the isomers preceding the ( most stable) spiro compounds. However, when the reactions were carried out at low temperature, isomers with less favourable heats of formation could b e trapped. We show that calculated heats of formation correspond well with synthetic yields and we suggest they can be a useful tool in planning synth eses.