cascade reactions to make polycyclic natural products
TRANSCRIPT
Cascade reactions to make polycyclic natural products
Brevetoxin Epoxy Cascade: Nakanishi, K. Toxicon 1985, 23, 473.
Squalene hopenecyclase (SHC)
(bacteria)
A Case Study in Biomimetic Total Synthesis: Polyolefin Carbocyclizations to Terpenes and SteroidsRyan A. Yoder and Jeffrey N. JohnstonChem. Rev., 2005, 105 (12), pp 4730–4756
OO
OO O O
OO
O
OO
HO
CHO
OH
B:
H
key intermediate inBrevetoxin B
Enantioselective polyene cyclization via Organo-SOMOCatalysis
OH
H
Me CN
Me
NH
NO
ArOH
H
Me CN
Me
-2 x 1e-
Cu(OTf)2,CH3CNNaTFA
-Mechanism of the reaction (draw the chair forms showing the allignment of orbitals),
-How does the chiral auxillary help in stereoselectivity,
-Why did slow addition of the oxidant increase the yield.
Note:- The mechanism involves formation of radical
CN
H
CN
Sebastian Rendler and David W. C. MacMillan J. Am. Chem. Soc. 2010, 131 ASAP
Enantioselective polyene cyclization via Organo-SOMOCatalysis
Sebastian Rendler and David W. C. MacMillan J. Am. Chem. Soc. 2010, 131 ASAP
Total synthesis of Omaezakianol
OHCl, ether rt, 14 h, 92% Cl
HO
HO
Cl
seperable 1:1
HO
Cl
Oxone, Bu4NHSO4CH2(OMe)2MeCN/H2OpH 10.5, 00C, 1.5 h
CSA , acetone, rt,21%
O O
O O O
HO
Cl
Na. ether 600C, 4 h, 76%
O O OH H H HO
OH O O O OCl
H H H HH OOH
HO
H2O
H+
Zhaoming Xiong, Robert Busch, E.J.Corey Org. Lett., 2010, 12 (7), pp 1512–1514
Total synthesis of ent-Dioxepandehydrothyrsiferol
Jessica Tanuwidjaja, Sze-Sze Ng and Timothy F. Jamison J. Am. Chem. Soc., 2009, 131 (34), pp 12084–12085
O
O
OH
HMe
H
Me
Br Me
Me
H
OMe
MeOH
Me H
OH
Total synthesis of ent-Dioxepandehydrothyrsiferol
Jessica Tanuwidjaja, Sze-Sze Ng and Timothy F. Jamison J. Am. Chem. Soc., 2009, 131 (34), pp 12084–12085
OH (a) L-(+)-DIPT, Ti(Oi-Pr)4, t-BuOOH 4 Angstrom MS CH2Cl2, -480C 88%, 82% ee
(b) TIPSCl, imidazole, CH2Cl2, rt, 90%(c) SeO2, salicylic acid, t BuOOH, CH2Cl2, rt, 73% (2 resubjections)(d) Ac2O, Et3N, DMAP, CH2Cl2, rt, 89%
OTIPSAcO
O
OHOO
(e) Shi Ketone 5, Oxone, Bu4NHSO4, K2CO3, Na2B4O7,pH 10.5, DMM/CH3CN/H2O, 00C, 30 min, 75% 3:1 dr; (f) LiOH, THF/MeOH/H2O rt, 84%,(g) (i) MsCl, Et3N, CH2Cl2, -78 to -100C; (ii) LiBr, THF, 0 to 80C, 1 h; (h) LiBEt3H, THF, -780C, 69% (3 steps); (i) TBAF, THF, rt 85%;99%;
(j) SO3.pyr, Et3N, DMSO, CH2Cl2, 00C to rt, 81%;(k) Ph3P=CHCO2Et, CH2Cl2, rt,(l) [(Ph3P)CuH]6, PhSiH3, THF 00C to rt, 95%(m)DIBAL-H, PhMe, -780C, 45 min, 73%'(n) Ph3P=C(CH3)CHO, C6H6 reflux, 64% > 95:5 E/Z(o) NaBH4, MeOH, 00C, 81%;
(p) L-(+)-DET, Ti(Oi-Pr)4, t-BuOOH 4 Angs. MS, CH2Cl2, -480C, 80% 95:5 dr;(q) Boc2O, NMI, PhMe, 00C to rt, 68%
OOOH
OOOBoc
OOO
O
O
O
O
Shi Ketone 5
Total synthesis of ent-Dioxepandehydrothyrsiferol
Jessica Tanuwidjaja, Sze-Sze Ng and Timothy F. Jamison J. Am. Chem. Soc., 2009, 131 (34), pp 12084–12085
OOOBoc
OO
O
OO
O OMeH
HMe
H
Me
Br Me
Me
H
NBS, HFIP4 Å MS
00C, 15 min
Give the mechanism
Total synthesis of ent-Dioxepandehydrothyrsiferol
Jessica Tanuwidjaja, Sze-Sze Ng and Timothy F. Jamison J. Am. Chem. Soc., 2009, 131 (34), pp 12084–12085
Total synthesis of ent-Dioxepandehydrothyrsiferol
Jessica Tanuwidjaja, Sze-Sze Ng and Timothy F. Jamison J. Am. Chem. Soc., 2009, 131 (34), pp 12084–12085
O
O
OO
O OMeH
HMe
H
Me
Br Me
Me
H
(a) NaOH, MeOH, rt, 83%(b) NaIO4, THF/H2O, rt 30 m,in. 96% O
O
OH
HMe
H
Me
Br Me
Me
H
O
(c) (SO2CF3)2NC5H3NCl, LHMDS, THF - 78 0C, Quant.;
O
O
OH
HMe
H
Me
Br Me
Me
H
OTf
Total synthesis of ent-Dioxepandehydrothyrsiferol
Jessica Tanuwidjaja, Sze-Sze Ng and Timothy F. Jamison J. Am. Chem. Soc., 2009, 131 (34), pp 12084–12085
OO Me
MeOH
Me H
OMe
MeOTES
Me H
OTES
(a)(CH3)3SI, n-BuLi, THF -13 to 50C, 73%
(b) TESCl, imidazole, DMF, rt, 95%
OMe
MeOTES
Me H
OTES
BBN
(c) 9-BBN dimer, THF, 600C, 20 h
Total synthesis of ent-Dioxepandehydrothyrsiferol
Jessica Tanuwidjaja, Sze-Sze Ng and Timothy F. Jamison J. Am. Chem. Soc., 2009, 131 (34), pp 12084–12085
O
O
OH
HMe
H
Me
Br Me
Me
H
OTf
OMe
MeOTES
Me H
OTES
BBN
(a) PdCl2(dppf), aq. Cs2CO3, THF/DMF/H2O 400C, 36 h, 78%(b) TBAF THF, rt, 83%
O
O
OH
HMe
H
Me
Br Me
Me
H
OMe
MeOH
Me H
OH
Mechanism
Total synthesis of (-)-FR182877
Natsumi Tanaka, Takahiro Suzuki, Takehiko Matsumura, Yosuke Hosoya, and Masahisa NakadaDOI: 10.1002/anie.200900097
-Isolated from Streptomyces sp. No. 9885.-Binds and stabilizes microtubules, exhibiting potent cytotoxic activity towards a number of human cancer cell lines comparable to Taxol.-Synthesized by Dr. Sorensen and Dr. Evans
Total synthesis of (-)-FR182877
Natsumi Tanaka, Takahiro Suzuki, Takehiko Matsumura, Yosuke Hosoya, and Masahisa NakadaDOI: 10.1002/anie.200900097
TBSO COOMe
OAcOTIPSOH
(a) TESCl, imidazole, CH2Cl2, rt, 30 min;(b) K2CO3, MeOH, rt, 30 min, 75% (2 steps:(c) MnO2, toluene, 800C, 2 d, 28%;
O
H
HH
H
TIPSO OTBS
H
H
H
COOMeOTES
O
H
HH
H
TIPSO OTBS
H
H
H
COOMeOTES