Late-stage diversification of chrysomycin A. (a) Synthesis of the
C2 glycosylated derivatives. (b) Synthesis of the C4 hybrid derivatives.
(c) Synthesis of the C3 hybrid derivatives via meta-selective C–H
functionalization. Reagents and conditions are as follows: (i) SnCl4, 4 Å MS, DCE, r.t. (ii) 1.5 M H2SO4 in MeOH, 70 °C. (iii) BCl3, CH2Cl2, −78 °C. (iv) NaOMe, MeOH, r.t. (v) POCl3, DMF, CHCl3, 70 °C. (vi) NaOClO, NaH2PO4, 2-methyl-2-butene, THF/tBuOH/H2O, r.t. (vii) 2-Propynylamine, HBTU, HOBt, DIPEA, DMF, r.t.
(viii) AlCl3, DCM, r.t. (ix) CuSO4, TBTA, sodium
ascorbate, DMF/tBuOH/H2O, r.t. (x) tert-butyl 2-iodobenzoate, L1, L2,
Pd(OAc)2, AgOAc, r.t. (xi) Pd/C, H2(3 MPa),
THF/MeOH, r.t.; PhNTf2, TEA, DCM, .r.t.; potassium vinyltrifluoroborate,
[Pd(dppf)Cl2]·CH2Cl2, Et3N, n-PrOH, reflux. (xii) 7.5% TFA, DCM, r.t.; prop-2-yn-1-amine,
HOBT, HBTU, DIPEA, DMF, r.t. (xiii) β-Glycosyl azides, CuSO4, TBTA, Na ascorbate, DMF/tBuOH/H2O, r.t.