UBC Theses and Dissertations
Macrolides : chemistry and progress towards a catalytic antibody Spracklin, Douglas K.
As part of a continuing study examining the chemistry and conformational behaviour of keto 13-tetradecanolides, 11 -oxo- 13-tetradecanolide (24) was synthesized. In the preparation of the acyclic precursor, optimal yields were obtained when the C-11 ketone was protected until the macrocyclic ring had been formed. Otherwise, a protected β-hydroxy group was eliminated under both acidic and basic conditions. The cyclization was accomplished via a trichlorobenzoyl chloride intermediate. Reduction of 24 using lithium tri-sec-butylborohydride (L-Selectride) gave the (11R* , 13S*)isomer of 49 in >99.8% diastereoselectivity. The relative stereochemistry of 49 was determined by reduction and conversion of the 1,3-diol to an acetonide for ¹³C NMR analysis. Molecular mechanics calculations were used to determine the possible low energy conformations for compounds 24 and 49. Reduction of 24 from the preferred twist  conformations would be expected to give rise to product 49 as is indeed observed. The calculations also predicted ¹H NMR coupling constants in good agreement with the observed values for both 24 and 49. [chemical compound diagrams] As part of an effort to develop a catalytic antibody for the synthesis of macrocyclic lactones, polyclonal antibodies against the phosphonate hapten 130 were raised. These antibodies demonstrated hapten-specific binding, but they did not catalyze the lactonization of a corresponding hydroxy ester substrate under the conditions examined. [chemical compound diagrams]
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