Template-Directed Condensations between Acyl Units

Abstract

<p>Glycoluril 1 acts as a bifunctional template, allowing efficient and repetitive<br />Claisen-type condensations between attached acyl units. Thus acetoacetyl<br />derivative 3 was prepared from 1 via 2. After conversion to the crotonate<br />derivative 4 (2 steps, β-carbonyl reduction and dehydration), a second cycle of<br />acylation and condensation gave crotonyl-transferred product 5. Repetition ofthe<br />sequence gave the 8-carbon derivative 6. Reduction of 4 with L-Selectride<br />afforded the butyryl derivative 7. allowing further acetylation and condensation<br />reactions leading towards long fatty acid chains. The product ratio from<br />condensation of the acetyl butyryl derivative of 1 is 4:1 in favour of deprotonation<br />of the acetyl group and transfer of the butyryl group. Reaction of 7 with lithium<br />benzyloxide gave recovered 1 and benzyl butyrate. Treatment of crotonyl acetyl</p> <p>[diagram removed]</p> <p>derivative 8 with L-Selectride produced only the acetyl transferred condensation<br />product 9. A similar regioselectivity was observed with L-Selectride reduction of<br />other α,β-unsaturated compounds (e.g., the acetyl acryloyl derivative). Results<br />of isotopic-labelling experiments support an intramolecular acyl transfer<br />mechanism for these condensations. This system mimics some of the features of polyketide and fatty acid synthases, allowing intramolecular acyl transfer and<br />repetitive additions of acetate units to make linear carbon chains while the<br />growing chain remains attached to the template. This is a potentially useful<br />method for the synthesis of some natural products and some useful organic<br />intermediates, such as putative oligoketide biosynthetic precursors.</p>