Enantioselective Total Synthesis of (-) Jiadifenolide Xu, J; - - PowerPoint PPT Presentation

▶
enantioselective total synthesis of jiadifenolide
SMART_READER_LITE
LIVE PREVIEW

Enantioselective Total Synthesis of (-) Jiadifenolide Xu, J; - - PowerPoint PPT Presentation

Aug 09, 2023 420 likes •537 views

Sarang Kulkarni Current Literature Presentation April 9, 2011 Enantioselective Total Synthesis of (-) Jiadifenolide Xu, J; Trzoss, L; Chang, W. K; Theodorakis, E. A Angew. Chem. Int. Ed. 2011 , 50 , 3672-3676 Sarang Kulkarni

slide-1
SLIDE 1

Sarang Kulkarni Current Literature Presentation April 9, 2011

Enantioselective Total Synthesis

  • f (-) Jiadifenolide

Xu, J; Trzoss, L; Chang, W. K; Theodorakis, E. A

  • Angew. Chem. Int. Ed. 2011, 50, 3672-3676

Sarang Kulkarni @ Wipf Group Page 1 of 9 4/16/2011

slide-2
SLIDE 2

Jiadifenolide and Related Natural Products

Kubo, M.; Okada, C.; Huang, J-M.; Harada, K.; Hioki, H.; Fukuyama, Y. Org. Lett. 2009, 11, 5190 Yokoyama, R.; Huang, J-M.; Yang, C.S.; Fukuyama, Y. J. Nat. Prod. 2002, 65, 527 Cho, Y. S.; Carcache, D. A.; Tian, Y.; Li, Y. L.; Danishefsky, S. J. J. Am. Chem. Soc. 2004, 126, 14358 Carcache, D. A.; Cho, Y. S.; Hua Z.; Tian, Y.; Li, Y. L.; Danishefsky, S. J. J. Am. Chem. Soc. 2006, 128, 1016

O O O O OH OH O (- )-Jiadifenolide O O OH O O CO2M e HO jiadifenin

  • Isolated from the pericarps of Illicium jiadif engpi by Fukuyam a and c o-work er s in 2009
  • Highly oxygenated pentacy clic cage s tr uc tur e
  • Pr om oter of neurite growth
  • Potential therapeutic v alue for neurodegener ative diseas es
  • Isolated fr om the per icarps of Illic ium jiadif engpi by Fukuyama and co-wor kers in 2002
  • First total s ynthesis by Danishefs ky and c o-work er s
  • B iologic al studies s howed J iadifenin upregulates the action of NGF (Nerv e growth factor)

O O OH O J iadifenoxolane A Jiadif enoxolane B Noemajucin A nisatin O O HO O O OH O O HO O O O OH O O HO HO H O OH O HO HO H O O HO Sarang Kulkarni @ Wipf Group Page 2 of 9 4/16/2011

slide-3
SLIDE 3

Oxidative Conversion of Neomajucin to Jiadifenolide

Kubo, M.; Okada, C.; Huang, J-M.; Harada, K.; Hioki, H.; Fukuyama, Y. Org. Lett. 2009, 11, 5190

O O OH O O HO HO H Dess- Martin P er iodinane O O OH O O HO O H+ O O O HO O OH O H+

  • H2O

O O O O OH O O O O O O O O O O OH O O O O O OH OH O O H2O H+ OH H+ Neom ajucin J aidifenolide Sarang Kulkarni @ Wipf Group Page 3 of 9 4/16/2011

slide-4
SLIDE 4

Retrosynthesis

O O O O OH OH O Jaidifenolide (1) 2 3 O O O OH O OTES O O O O OH O OTES O TBSO OH O O O O TBSO O O O 6 5 4 Xu, J; Trzoss, L; Chang, W. K; Theodorakis, E. A Angew. Chem. Int. Ed. 2011, 50, 3672

Sarang Kulkarni @ Wipf Group Page 4 of 9 4/16/2011

slide-5
SLIDE 5

Synthesis of tricyclic lactone 5

Ruprah, P. K.; Cros, J-P.; Pease, J. E.; Whittingham, W. G.; Williams, J. M. J. Eur. J. Org Chem. 2002, 3145-3152 Zhang, X-M.; Wang, M.; Tu, Y-Q.; Fan, C-A.; Jaing, Y-J.; Zhang, S-Y, Zhang, F-M. Synlett, 2008, 18, 2831-2835

O O

  • 1. Pd[(C3H5)Cl2]2

dppe, ally l acetate B SA , NaOAc

  • 2. MV K, Ac OH, H2O

63%, 2 Steps O O O D-prolinamide (30 mol%) PP TS (30 mol%) MeCN, 14 days 74%, >90% ee O O 7 8 6

  • 1. NaB H4 E tO H
  • 2. TBS Cl. NH4NO3

DMF, 92% 2 S teps T BSO O then, E t3O+BF4- 1.

  • 2. TM SOT f, 2,6-Lutidine

then TBA F, M eI 43%, 2 S teps TBS O O O OEt

  • 1. LiA lH4
  • 2. TB SCl, Im
  • 3. IB X

85%, 3 S teps T BSO O OTB S

  • 1. K HM DS, PhNTf2
  • 2. CO (1 atm )

[Pd(P Ph3)4] ( 1 m ol%) NEt3 then, TFA, CH2Cl2 69%, 2 Steps TBS O O O 9 10 11 5 H3CO O OM gOCH3 Sarang Kulkarni @ Wipf Group Page 5 of 9 4/16/2011

slide-6
SLIDE 6

O O Base, RX , s olvent O O R O OR A B R X Conditions Yield % (A) M e I NaOH/H2O/diox ane reflux 35 I T lOE t/M eI, 41 C 5 CH2CH=CHC2H5 Cl K OH/H2O 41 CH2C CC2H5 Br Na2CO3/H2O/PTC 65 O NaH, CO2 O 25-45% O O O H3CO O OM gOCH3 H+ 41-64% Sc hick, H.; E ic hhorn, I. Sy nthes is , 1989, 477-492 M ec heli, R. A .; Hajos, Z. G.; Cohen, N.; Parr ish, D. R.; Portland, L. A .; S ciam anna, W .; Sc ott, M. A.; Wehrli, P. A. J . Or g. Chem. 1975, 40, 675-681 COOH Mg O O COOH Sarang Kulkarni @ Wipf Group Page 6 of 9 4/16/2011

slide-7
SLIDE 7

Synthesis of Lactone 14

TB SO O O 5 12 4 H2O2, 3 M NaOH TB SO O O O 99%

  • 1. OsO4 (1 mol%)

NaIO4

  • 2. Jones r eagent

70% (2 Steps ) TBSO O O O H O O X - ray, 4.5 g T BAF 95% HO O O O H O O

  • 1. mCP BA
  • 2. Des s-M ar tin Periodinane

38%, 2 Steps O O O O OH O OH 13 14 mCP BA HO O O O H O O O DM P H+ O O O OH O O O H H Sarang Kulkarni @ Wipf Group Page 7 of 9 4/16/2011

slide-8
SLIDE 8

Completion of the Synthesis

Hirota, K.; Isobe, Y.; Maki, Y. J. Chem. Soc. Perkin Trans 1, 1989, 2513 Davis, F. A.; Chattopadhyay, S.; Towson, J. C.; Lal, S.; Reddy, T. J. Org. Chem. 1988, 53, 2087

O O O O OH O OH 14 15 16

  • 1. H2, 10% Pd/C
  • 2. T ESO Tf

2,6-Lutidine 90%, 2 Steps O O O O O H O O TES

  • 1. KHM DS

Comins r eagent

  • 2. AlMe3, [P d(PP h3)4]

57%, 2 S teps O O O O H O O TES

  • 1. H2, P tO 2
  • 2. NaHM DS

Dav is oxaziridine O O O O H O O TES OH Jones r eagent O O O O O H OH O Jaidifenolide (1) 17 N Cl N Tf Tf Comins Reagent N O PhO2S H Ph Davis Oxaz iridine Sarang Kulkarni @ Wipf Group Page 8 of 9 4/16/2011

slide-9
SLIDE 9

Conclusions

  • First total synthesis of (-)-jiadifenolide, in 1.5% overall

yield and 25 total steps

  • Acid-induced cascade reaction to setup desired lactone
  • Gram scale synthesis of tetracyclic lactone 4, can be

used in synthesis of related natural products and analogs

Sarang Kulkarni @ Wipf Group Page 9 of 9 4/16/2011