Avermectins aglycone

In the synthesis of avermectin Bla, the disaccharide fluoride 48 is prepared and coupled with avermectin aglycon 49 in the presence of SnCl2-AgC104 in dry ether to give protected avermectin Bla50 in 62% yield (Scheme 2.16) [23]. 

Ri is located at C23 of the avermectin aglycone. Where R-, is absent, the C22.23 double bond is present. R2 is part of either a sec-butyl or an isopropyl group attached to C25. R3 is part of either a methoxy or a hydroxyl group at C5. The two O-methylated oleandrose residues are located at C13. 

Coupling of Disaccharide Fluoride 4 with Avermectin Aglycon 5 To a suspension of AgC104 (12 rag, 0.06 mmol), SnCl2 (11 mg, 0.06 mmol), and crushed 4-A molecular sieves (100 mg, dried) in dry ether (3.5 mL) under argon at — 15°C was added alcohol 5 (52 mg, 0.074 mmol) in ether (1 mL). A solution of the disaccharide fluoride 4 (24 mg, 0.057 mmol) in ether (1 mL) was added and stirring was continued at 0°C for 16 h. The reaction mixture was diluted with ether (30 mL) and filtered through Celite. The filtrate was washed with saturated aqueous NaHCOj solution (5 mL) and brine (5 mL),... 

In avermectin polyketide synthase, the last invariant Ala in the motif sequence is substituted to Thr [28]. KR domain activity is predicted to be required for the formation of avermectin aglycons. In another group of KR domains, the motif sequence corresponding region is not found, which readily accounts for their inactivity. 

The formation of avermectin aglycons involves KRs that resemble type I and II FAS. The C5-keto group is reduced by a monofunctional KR (AveF) that is not within module 11 of the AVES 4 (Fig. 10). The mutants defective in C5 ketore-ductase gene, aveF, which were obtained by introducing an insertion mutation in the promoter region of aveD-aveF operon produced 5-oxoavermectins [104]. 

Scheme 29.6.4. Activity of avermectin aglycone derivatives against Tetranychus urticae R = C2H5 (>80%) and CH3 (<20%).

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