A full account of semisyntheses of polychlorinated marine steroids clionastatins A and B is described.We have developed a unique two-stage chlorination-oxidation strategy that enabled concise and divergent semisynthes...A full account of semisyntheses of polychlorinated marine steroids clionastatins A and B is described.We have developed a unique two-stage chlorination-oxidation strategy that enabled concise and divergent semisyntheses of clionastatins A and B in 16 steps from inexpensive testosterone.Key transformations in chlorination stage include(a)conformationally controlled,stereospecific dichlorination through an unusualβ-chloronium intermediate to install the diequatorial C1,C2-dichloride;(b)C4-OH directed C19–H oxygenation followed by challenging neopentyl chlorination to install the C19–Cl.The high oxidation level was constructed through(a)the desaturation at C6–C7 through one-pot photochemical dibromination–reductive debromination;(b)regioselective anti-Markovnikov oxidation of the C6–C7 double bond by photoredox-metal dual catalysis to forge the B ring enone;(c)late-stage desaturation with SeO_(2)to introduce C8–C9 double bond.Wharton transposition was used to forge the D-ring enone,and thermodynamically driven epimerization secured the cis-fused C/D ring system.Furthermore,we also provided a 14-step approach to clionastatin A by optimizing the construction of the D-ring enone with a dehydration-oxidation sequence.展开更多
基金Financial support from the National Natural Science Foundation of China(Nos.22071205 and 21772164)NFFTBS(J1310024)+1 种基金NCETFJ,and PCSIRT is acknowledged.The authors are also grateful for the financial support(LMDBKF-2019-03)the Laboratory for Marine Drugs and Bioproducts,Pilot National Laboratory for Marine Science and Technology.
文摘A full account of semisyntheses of polychlorinated marine steroids clionastatins A and B is described.We have developed a unique two-stage chlorination-oxidation strategy that enabled concise and divergent semisyntheses of clionastatins A and B in 16 steps from inexpensive testosterone.Key transformations in chlorination stage include(a)conformationally controlled,stereospecific dichlorination through an unusualβ-chloronium intermediate to install the diequatorial C1,C2-dichloride;(b)C4-OH directed C19–H oxygenation followed by challenging neopentyl chlorination to install the C19–Cl.The high oxidation level was constructed through(a)the desaturation at C6–C7 through one-pot photochemical dibromination–reductive debromination;(b)regioselective anti-Markovnikov oxidation of the C6–C7 double bond by photoredox-metal dual catalysis to forge the B ring enone;(c)late-stage desaturation with SeO_(2)to introduce C8–C9 double bond.Wharton transposition was used to forge the D-ring enone,and thermodynamically driven epimerization secured the cis-fused C/D ring system.Furthermore,we also provided a 14-step approach to clionastatin A by optimizing the construction of the D-ring enone with a dehydration-oxidation sequence.
