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J. Braz. Chem. Soc., Vol. 21, No. 10, 2012-2016, 2010.
Printed in Brazil - ©2010 Sociedade Brasileira de Química 0103 - 5 05 3 $ 6.00+ 0.00
* e-mail: ldias@ iq m.unicamp .b r
Total Synthesis of
(−)
-Basiliskamide A and NMR Studies on the Conversion of
Basiliskamide A to Basiliskamide B
Luiz C. Dias* and Caroline C. S. Gonçalves
Instituto de Química, Universidade Estadual de Campinas, CP 61 5 4 , 1 3 0 8 3 - 9 7 0 Campinas- SP, Brazil
D escrev emos neste trab alh o nossa rota sintética p ara ob tenção do p olicetídeo antif úng ico (−) -b asilisk amida A , assim como estudos de R M N de 1H relacionados a mig ração da cadeia lateral
cinamoíla da b asilisk amida A p ara f ormar a b asilisk amida B em C D C l3.
W e describ e h erein our ap p roach to th e total sy nth esis of th e antif ung al p oly k etide (−)-b asilisk amide A , as w ell as 1H NM R studies on th e mig ration of th e cinnamoy l side ch ain of
b asilisk amide A to f orm b asilisk amide B in C D C l3 solution.
Keywords: antif ung al p oly k etides, Stille cross-coup ling , aldol reaction, NM R studies
Introduction
T h e p oly k etides b asilisk amides A (1) and B (2) w ere isolated f rom th e marine b acterium PNG -27 6 f rom th e coast of Pap ua New G uinea ( F ig ure 1) .1,2 T h ese antif ung al
p oly k etides sh ow p otent in vitro activ ity ag ainst Candida alb icans and A sperg illus f umig atus,1 as w ell as at least
4 -f old less cy totox icity f or normal h uman f ib rob last cells w h en comp ared to amp h otericin B.1,3 T h e relativ e
conig urations of b asilisk amides A (1) and B (2) w ere p rop osed b y A ndersen and co-w ork ers1 and th e ab solute
conig urations h av e b een conirmed b y total sy nth esis.4
W e h av e recently concluded th e total sy nth esis of b asilisk amide B.5 A s th e natural sup p ly of b asilisk amide
A is restricted, and attracted b y its p otent cy totox icity , w e initiated a p roj ect directed tow ards an ef icient and lex ib le
total sy nth esis, in order to p rov ide f urth er material f or more ex tensiv e b iolog ical studies, along w ith access to nov el analog s.6
Results and D iscussion
O ur ap p roach f or th e p rep aration of (−) -b asilisk amide A (1) b eg an w ith th e sy nth esis of v iny l iodide 4, p rep ared in 7 step s and 19 .1% ov erall y ield f rom eth y lk etone 3 ( Sch eme 1) .5 ,7
T h e nex t step inv olv ed a Stille cross-coup ling reaction b etw een Z-v iny lstannane 58 and E-v iny l iodide 4
( Sch eme 2) . T h is w as accomp lish ed b y treatment of 4 and 5 in D M F w ith cataly tic amounts of Pd( M eC N)2C l2 at 5 0 oC ,
p rov iding 6 in 60% y ield af ter p uriication b y silica-g el column ch romatog rap h y .A t th is p oint only f our sy nth etic op erations remained to conclude th e total sy nth esis of
(−) -b asilisk amide A . R emov al of th e isop rop y lidene acetal p rotecting g roup in 6 w ith 8 0% A cO H p rov ided diol 7. Selectiv e p rotection of th e less h indered ox y g en w ith T E S ch loride in th e p resence of p y ridine g av e alcoh ol
8 ( 67 % y ield, 2 step s) .9 T reatment of secondary alcoh ol
H2N
O
OH O
Me Me Me
basiliskamide A (1) O
Ph O
Me OH
Me O
basiliskamide B (2) Me H2N
O
Ph
D ias and G onçalv es 2013 Vol. 21, No. 10, 2010
8 w ith E-cinnamoy l ch loride in th e p resence of D M A P
and E t3N g av e ester 9, w h ich , af ter treatment w ith H F in acetonitrile, p rov ided (−) -b asilisk amide A in 4 2% f or th e f our-step seq uence.
T h e sp ectroscop ic and p h y sical data (1H and 13C NM R ,
I R , [α]D, R
f) f or sy nth etic (−) -b asilisk amide A w ere
identical in all resp ects w ith th e p ub lish ed data for th e natural p roduct.1,4
N M R studies
A t th is p oint, w e decided to inv estig ate th e p ossib ility of b asilisk amide B b eing p roduced b y cinnamoy l side ch ain mig ration f rom b asilisk amide A . T o th is end, w e did an NM R study to v erif y w h eth er th e conv ersion of b asilisk amide A to b asilisk amide B in mild acidic C D C l3 solution w as p ossib le or not ( Sch eme 3) . T h is conv ersion w ould occur th roug h mig ration of th e cinnamoy l side ch ain
f rom th e more h indered ox y g en at C 9 in b asilisk amide A to th e less h indered ox y g en at C 7 .
I n th e 1H NM R sp ectrum of b asilisk amide A (1) , th e
sig nal at d 3.63 p p m ( dt, J 3.5 and 10.0 H z) is attrib uted to
th e h y drog en H 7 . I n th e 1H NM R sp ectrum of b asilisk amide
B th e sig nal at d 3.35 p p m ( dd, J 2.5 and 9 .5 H z) ref ers to
th e h y drog en H 9 ( F ig ure 2) .
A f ter 24 h , th e 1H NM R sp ectrum of b asilisk amide A (1)
sh ow s a new sig nal at d 3.35 p p m, w h ich corresp onds to th e h y drog en H 9 of b asilisk amide B ( F ig ure 3) . A f ter 20 day s, w e can ob serv e th at th e sig nal at d 3.35 p p m increases leading to a 1.00: 0.4 5 ratio of b asilisk amide A (1) and b asilisk amide B (2) , resp ectiv ely . T h is clearly sh ow s th at th e mig ration of th e cinnamoy l side ch ain is occurring and th at it is p ossib le th at b asilisk amide B is an artif act of b asilisk amide A .10
Conclusions
I n summary , a h ig h ly conv erg ent and ef icient total sy nth esis of (−) -b asilisk amide A h as b een accomp lish ed. T h e sy nth esis req uired 15 step s f rom eth y lk etone 3 and p roduced th e desired p roduct in 3.2% ov erall y ield. T h is ap p roach comp ares v ery w ell w ith th e p ub lish ed routes to (−) -b asilisk amide A4 and th e sy nth etic strateg y p resented
h ere is, in p rincip le, readily ap p licab le f or th e p rep aration of additional analog ues.
O Me OPMB Me 3 9 5 9 O Me O
4 (E:Z = 88:12) I Me Me Me Me Ref. 5
Scheme 1 . Sy nth esis of v iny l iodide 4 f rom of eth y lk etone 3.
O Me OH Me O Me H2N
3 4 9 7 1 4 80% AcOH
60 oC, 3 h
Pd(MeCN)2Cl2
H2N O H SnBu3 1 5 + 1 5 9 6 H2N
O O Me O Me Me DMF, 50 oC
O O Me 9 Me I Me Me Me Me Me
H2N
O O O Me Me Me 9 O Ph
H2N
O
OH O
Me Me Me
basiliskamide A (1) O
Ph
HF, CH3CN
42% (4 steps)
1 7 9
1 7 9
(E)-cinnamoyl chloride
DMAP, Et3N, CH2Cl2
TES TES 8 60% 1 5 9 7 H2N
O OH Me OH Me Me TESCl, pyridine
25 oC, 67%
(2 steps)
T otal Sy nth esis of ( –) -Basilisk amide A and NM R Studies on th e C onv ersion of Basilisk amide A to BJ. Braz. Chem. Soc. 2014
Scheme 3 . C innamoy l side ch ain mig ration of b asilisk amide A .
OH O
Me Me Me
basiliskamide A (1) O Ph O Me OH Me O
basiliskamide B (2)
1
5 9 Me
H2N
O
Ph H2N
O 1 5 9 H+ CDCl3 solution H O O H Me O H R1 H R2 7 9 H
R1 =
Me
Me
R2 = O
NH2
#
forming bond breaking bond
Ph
F ig ure 2 . C h emical sh if ts in th e 1H NM R sp ectrum ( C D C l
3, 5 00 M H z) of H 7 in b asilisk amide A (1) and H 9 in b asilisk amide B (2) .
E x p erimental
(−) - Basilisk amide A (1)
T h e diene 6 ( 68 .5 mg , 0.23 mmol) w as dissolv ed in 8 0% acetic acid ( 5 mL ) . T h e reaction w as p rotected f rom lig h t and stirred at 60 oC f or 3 h . T h e reaction w as th en allow ed
to reach amb ient temp erature and adj usted to p H 7 .0 w ith
NH4O H . T h e aq ueous p h ase w as ex tracted w ith E tO A c ( 2 × 10 mL ) , th e comb ined org anic ex tracts w ere dried ov er
M g SO4, iltered and concentrated under reduced p ressure
to g iv e th e corresp onding diol 7. Rf = 0.15 ( h ex ane: E tO A c, 5 0: 5 0) . [α]D25 = +15 (c = 0.35 , C H C l
3) .
1H NM R ( D M SO -d
6, 25 0 M H z) :d 0.69 ( d, 3H , J 7 .0 H z) ; 0.7 3 ( d, 3H , J 6.3 H z) ;
0.8 4 ( t, 3H , J 7 .3 H z) ; 1.35 ( m, 3H ) , 1.61 ( m, 1H ) ; 2.05 ( m,
1H ) ; 2.28 ( m, 1H ) ; 3.24 ( m, 1H ) ; 3.8 1 ( m, 1H ) ; 4 .4 9 ( d, 1H ,
J 5 .3 H z) ; 4 .7 ( d, 1H , J 4 .7 H z) ; 5 .5 8 ( d, 1H , J 5 .6 H z) ; 6.03
( dt, 1H , J 6.0 H z) ; 6.37 ( t, 1H , J 11.5 H z) ; 6.8 6 ( b rs, 1H ) ;
7 .37 ( b rs, 1H ) ; 7 .4 5 ( dd, 1H , J 11.5 e 15 .5 H z) . 13C NM R
( D M SO -d6, 62.5 M H z) :d 11.3; 12.4 ; 12.5 ; 27 .22; 35 .9 ; 36.8 ; 4 1.9 ; 7 1.9 ; 7 4 .8 ; 119 .6; 128 .5 ; 14 1.2; 14 1.3; 168 .1. I R ( ilm)
νmax/ cm-1: 335 0, 29 64 , 29 30, 28 7 1, 1666, 14 5 4 , 1327 . H R M S:
[C14H26NO3+] : ex p ected: 25 6.19 07 ; ob serv ed: 25 6.19 13.
A solution of th e corresp onding crude diol 7 ob tained
b ef ore ( 4 4 .8 mg ; 0.18 mmol) in p y ridine ( 3 mL ) w as treated w ith T E SC l ( 0.033 mL ; 0.19 mmol) at 0 oC , and stirred at
25 oC f or 2 h . T h e reaction w as q uench ed w ith aq ueous
saturated NaHC O3 solution and ex tracted w ith E tO A c p rov iding alcoh ol 8. Rf = 0.4 ( h ex ane: E tO A c, 5 0: 5 0) .
1H NM R ( C
6D6, 25 0 M H z) :d 0.7 3 ( q , 6H , J 8 H z) ; 0.8 4
( d, 3H , J 6.8 H z) ; 1.01 ( m, 6H ) ; 1.12 ( t, 9 H , J 8 H z) ; 1.4 9
( m, 3H ) ; 2.02 ( m, 1H ) ; 2.4 3 ( t, 2H , J 6.3 H z) ; 2.67 ( b rd,
OH O
Me Me Me
basiliskamide A (1) O Ph O Me OH Me O
basiliskamide B (2)
1
5 9 Me
H2N
O
Ph H2N
O 1 5 9 H+ CDCl3 solution H O O H Me O H R1 H R2 7 9 H
R1 =
Me
Me
R2 = O
NH2
#
forming bond
breaking bond
D ias and G onçalv es 2015 Vol. 21, No. 10, 2010
F ig ure 3 . Partial 1H NM R sp ectrum ( C D C l
3, 5 00 M H z) sh ow ing th e mig ration of th e cinnamoy l side ch ain af ter 24 h and af ter 20 day s.
1H , J 3.3 H z) ; 3.4 4 ( b rd, 1H , J 8 .5 H z) ; 4 .23 ( q , 1H , J 5 .3
H z) ; 4 .7 2 ( b rs, 1H ) ; 5 .19 ( d, 1H , J 11.3 H z) ; 5 .5 9 ( b rs, 1H ) ;
6.25 ( dt, 1H , J 7 .3 e 15 .5 H z) ; 6.39 ( t, 1H , J 11.3 H z) ; 8 .17
( dd, 1H , J 11.5 e 15 .3 H z) .13C NM R ( C
6D6, 62.5 M H z) :
d 5 .5 ; 7 .2; 11.3; 11.8 ; 12.4 ; 27 .6; 36.8 ; 37 .2; 4 2.1; 7 5 .2; 7 5 .6; 118 .2; 129 .6; 14 1.1; 14 2.6; 168 .1.
T h e crude alcoh ol 8 ( 0.029 mmol) in C H2C l2 ( 0.7 mL ) w as treated w ith E t3N ( 0.034 mL ; 0.24 mmol) and D M A P ( 1.7 mg , 0.014 mmol) and cooled to 0 oC . T h e solution w as
treated w ith (E) -cinnamoy l ch loride ( 0.02 g ; 0.12 mmol) .
T h e reaction w as p rotected f rom lig h t and stirred at amb ient
temp erature f or 18 h , and th e reaction w as th en q uench ed w ith w ater. T h e aq ueous p h ase w as ex tracted w ith C H2C l2 and th e solv ent w as remov ed under reduced p ressure to p rov ide ester 9. Rf = 0.5 5 ( E tO A c: C H2C l2, 4 0: 10) . [α]D25 = −7 7 (c 0.26, M eO H ) . 1H NM R ( C D C l
3, 5 00 M H z) : d 0.8 3 ( d, 3H , J 7 .0 H z) ; 0.8 4 ( d, 3H , J 7 .0 H z) ; 0.8 7 ( t, 3H , J 7 .5 H z) ; 0.9 0 ( d, 3H , J 7 .0 H z) ; 1.11 ( m, 1H ) 1.25 ( m,
1H ) ; 1.67 ( m, 1H ) ; 1.9 9 ( m, 1H ) ; 2.06 ( m, 1H ) ; 2.28 ( m, 1H ) ; 3.4 9 ( m, 1H ) ; 4 .5 7 ( d, 1H , J 5 .0 H z) ; 4 .9 2 ( dd, 1H ;
J 2.0 e 9 .5 H z) ; 5 .5 5 ( d, 1H , J 11.0 H z) ; 5 .9 1 ( dt, 1H , J 7 .0 e
15 .0 H z) ; 6.31 ( b rt, 1H , J 11.0 H z) ; 6.61 ( d, 1H , J 16.0 H z) ;
6.8 3 ( s, 1H ) ; 7 .31 ( s, 1H ) ; 7 .4 0 ( dd, 1H , J 11.0 e 15 .0 H z) ;
7 .4 1 ( m, 2H ) ; 7 .65 ( d, 1H , J 16.0 H z) ; 7 .7 1 ( m, 2H ) .
13C NM R ( C D C l
3, 100 M H z) :d 10.1; 11.6; 12.8 ; 26.4 ; 34 .7 ;
35 .5 ; 4 0.8 ; 69 .7 ; 7 6.3; 118 .0; 119 .3; 128 .2; 128 .4 ; 128 .9 ;
130.4 ; 134 .0; 14 0.5 6; 14 0.5 8 ; 14 4 .6; 166.1; 167 .5 . I R ( ilm)
νmax/ cm-1: 3367 , 29 66, 29 36, 17 01, 167 0, 15 8 8 .
T h e crude comp ound 9 ( 0.029 mmol) w as treated w ith 0.4 mL of a solution of H F ( 4 0% aq ueous solution) : C H3C N ( 1: 18 ) . A f ter 10 min at r.t. th e reaction w as q uench ed w ith NaH C O3 ( 4 mg ) and stirred f or 10 min, iltered and concentrated in vacuo. Puriication b y lash column ch romatog rap h y ( E tO A c: C H2C l2, 4 : 2) af f orded (−) -b asilisk amide A (1) ( 4 .6 mg , 4 2% y ield, 4 step s) . Rf = 0.6 ( E tO A c: C H2C l2, 4 0: 10) . 1H NM R ( D M SO -d
6, 5 000
M H z) : d 7 .7 2 ( 2H , m) ; 7 .66 ( 1H , d, 16.0 H z) ; 7 .4 1 ( 3H , m) ; 7 .4 1 ( 3H , m) ; 7 .39 ( 1H , m) ; 7 .33 ( 1H , b rs) ; 6.8 4 ( 1H , b rs) ; 6.62 ( 1H , d, 16.0 H z) ; 6.31 ( 1H , ap t, 11.5 H z) ; 5 .91 ( 1H , dt,
7 .4 and 14 .9 H z) ; 5 .5 5 ( 1H , d, 11.5 H z) ; 4 .9 2 ( 1H , dd, 2.6 and 9 .5 H z) ; 4 .5 8 ( 1H , d, 5 .4 H z) ; 3.4 8 ( 1H , m) ; 2.28 ( 1H , m) ; 2.02 ( 1H , m) ; 2.02 ( 1H , m) , 1.67 ( 1H , m) ; 1.25 ( 1H , m) ; 1.11 ( 1H , m) ; 0.8 9 ( 3H , d, 6.6 H z) ; 0.8 7 ( 3H , t, 7 .7 H z) ; 0.8 4 ( 3H , d, 7 .1 H z) p p m. 13C NM R ( D M SO -d
6, 125 M H z) : d 167 .5 ; 166.1; 14 4 .6; 14 0.5 6; 14 0.5 1; 134 .0; 130.4 ; 128 .9 ; 128 .4 ; 128 .3; 119 .4 ; 118 .0; 7 6.3; 69 .7 ; 4 0.8 ; 35 .5 ; 34 .7 ; 26.4 ; 12.8 ; 11.7 ; 10.1 p p m.
Sup p lementary Information
T otal Sy nth esis of ( –) -Basilisk amide A and NM R Studies on th e C onv ersion of Basilisk amide A to BJ. Braz. Chem. Soc. 2016
Acknowledg ments
W e are g ratef ul to F A E P-U nicamp , F A PE SP
( F undação de A mp aro à Pesq uisa do E stado de São Paulo) , C NPq ( C onselh o Nacional de D esenv olv imento C ientíico e T ecnológ ico) and I NC T -I NO F A R Proc. C NPq 5 7 3.5 64 / 2008 -6 f or inancial sup p ort. W e also th ank Prof . C arol H . C ollins ( U nicamp ) , f or h elp f ul sug g estions ab out E ng lish g rammar and sty le, L eonardo J osé Steil ( U F A BC ) f or h elp f ul comments and Prof essor C arlos R oq ue D uarte C orreia ( U nicamp ) f or sug g estions and comments ab out th e NM R studies.
References
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2 0 0 5 / 0 2 7 7 7 7 9 A 1, 2 0 0 5.
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2 0 0 5, 1 4 0 C, 265 .
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1 9 9 6, 4 9, 34 5 ; O k ada, Y .; M atsunag a, S.; v an Soest, R . W .
M .; F usetani, N.; O rg . L ett. 2 0 0 2, 4, 3039 ; M oh ap atra, D . K .; C h audh uri, S. R .; Sah oo, G .; G urj ar, M . K .; T etrahedron: A sy mmetry 2 0 0 6, 1 7, 2609 ; F rederico, D .; C onstantino, M . G .;
D onate, P. M .; J. Braz. Chem. Soc. 2 0 0 9, 2 0, 8 8 8 ; A b aee, M . S.;
M oj tah edi, M . M .; F org h ani, S.; G h andch i, N. M .; F orouzani, M .; Sh arii, R .; C h ah arnazm, B.; J. Braz. Chem. Soc. 2 0 0 9, 2 0,
18 9 5 .
7 . T h e numb ering of 1 f ollow s th at sug g ested in ref erence 1.
8 . Stille, J . K .; G roh , B. L .; J. A m. Chem. Soc. 1 9 8 7, 1 0 9, 8 13; E sp inet, P.; E ch av arren, A . M .; A ng ew . Chem. Int. Ed. 2 0 0 4, 4 3, 4 7 04 ; F arina, V.; Pure A ppl. Chem. 1 9 9 6, 68, 7 3; F arina, V.; K rish nan, B.; J. A m. Chem. Soc. 1 9 9 1, 1 1 3, 9 5 8 5 ; Sing h , R .; Sh arma, M .; M amg aun, R .; R aw at, D . D .; J. Braz. Chem. Soc. 2 0 0 8, 1 9, 35 7 .
9 . D ias, L . C .; de Sousa, M . A .; T etrahedron L ett. 2 0 0 3, 4 4, 5 625 ; D ias, L . C .; de O liv eira, L . G .; de Sousa, M . A .; O rg . L ett. 2 0 0 3, 5, 265 ; D ias, L . C .; M eira, P. R . R .; T etrahedron L ett. 2 0 0 2, 4 3, 18 5 ; D ias, L . C .; M eira, P. R . R .; J. O rg . Chem. 2 0 0 5, 7 0, 4 7 62; D ias, L . C .; de O liv eira, L . G .; Vilcach ag ua, J . D .; Nig sch , F .; J. O rg . Chem. 2 0 0 5, 7 0, 2225 ; D ias, L . C .; F erreira, E .; T etrahedron L ett. 2 0 0 1, 4 2, 7 15 9 ; D ias, L . C .; F erreira, A . A .; D iaz, G .; Sy nlett 2 0 0 2, 18 4 5 ; D ias, L . C .; D iaz, G .; F erreira, A . A .; M eira, P. R . R .; F erreira, E .; Sy nthesis 2 0 0 3, 4, 603; D ias, L .
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10. W h en sub mitting (−) -b asilisk amide B to th e same ex p eriment w e can not ob serv e th e sig nal at d 3.63 p p m ( dt, J 3.5 and
10.0 H z) th at corresp onds to h y drog en H 7 of b asilisk amide A . H ow ev er, th e f ormation of anoth er comp ound th at sh ow s th ree w ell deined sig nals (d 3.65 , 4 .9 4 and 5 .04 p p m) w as ob serv ed.
Sub mitted: M ay 4 , 2 0 1 0
Pub lished online: A ug ust 3 , 2 0 1 0
Su
pp
le
m
enta
ry
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or
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ati
on
J. Braz. Chem. Soc., Vol. 21, No. 10, S1-S6, 2010.
Printed in Brazil - ©2010 Sociedade Brasileira de Química 0103 - 5053 $6.00+0.00
*e-mail: [email protected]
Total Synthesis of
(−)
-Basiliskamide A and NMR Studies on the Conversion of
Basiliskamide A to Basiliskamide B
Luiz C. Dias* and Caroline C. S. Gonçalves
Instituto de Química, Universidade Estadual de Campinas, CP 61 5 4 , 1 3 0 8 4 - 9 7 1 Campinas- SP, Brazil
Figure S1. 1H NMR of acetonide 6 (DMSO-d
Total Synthesis of (–)-Basiliskamide A and NMR Studies on the Conversion of Basiliskamide A to B J. Braz. Chem. Soc. S2
Figure S2. 13C NMR of acetonide 6 (DMSO-d
6, 62.5 MHz).
Dias and Gonçalves S3 Vol. 21, No. 10, 2010
Figure S4. 1H NMR of diol 7 (DMSO-d
6, 250 MHz).
Figure S5. 13C NMR of diol 7 (DMSO-d
Total Synthesis of (–)-Basiliskamide A and NMR Studies on the Conversion of Basiliskamide A to B J. Braz. Chem. Soc. S4
Figure S6. IR of diol 7.
Dias and Gonçalves S5 Vol. 21, No. 10, 2010
Figure S8. 1H NMR of basiliskamide A (1), (DMSO-d
6, 500 MHz).
Figure S9. 13C NMR of basiliskamide A (1), (DMSO-d
Total Synthesis of (–)-Basiliskamide A and NMR Studies on the Conversion of Basiliskamide A to B J. Braz. Chem. Soc. S6
Table 1. Comparison of 1H and 13C NMR data for natural1 and our synthetic basiliskamide A (DMSO-d
6)
1H NMR (400 MHz) d/ppm (number of hydrogens, multiplicity, coupling constant)
Natural
1H NMR (500 MHz) d/ppm (number of hydrogens, multiplicity, coupling constant)
Synthetic
13C NMR (100 MHz)1 d (ppm) Natural
13C NMR (125 MHz)1 d (ppm) Synthetic
0.84 (3H, d, 7.0 Hz) 0.84 (3H, d, 7.1 Hz) 10.1 10.1
0.87 (3H, t, 7.5 Hz) 0.87 (3H, t, 7.7 Hz) 11.6 11.7
0.90 (3H, d, 7.0 Hz) 0.89 (3H, d, 6.6 Hz) 12.8 12.8
1.11 (1H, m) 1.11 (1H, m) 26.4 26.4
1.25 (1H, m) 1.25 (1H, m) 34.7 34.7
1.67 (1H, m) 1.67 (1H, m) 35.5 35.5
1.99 (1H, m) 2.02 (1H, m) 40.7 40.8
2.06 (1H, m) 2.04 (1H, m) 69.6 69.7
2.28 (1H, m) 2.28 (1H, m) 76.3 76.3
3.49 (1H, m) 3.48 (1H, m) 118.0 118.0
4.57 (1H, d, 5.0 Hz) 4.58 (1H, d, 5.4 Hz) 119.3 119.4
4.92 (1H, dd, 2.0 and 9.5 Hz) 4.92 (1H, dd, 2.6 and 9.5 Hz) 128.2 128.3
5.55 (1H, d, 11.0 Hz) 5.55 (1H, d, 11.5 Hz) 128.4 128.4
5.91 (1H, dt, 7.0 and 15.0 Hz) 5.91 (1H, dt, 7.4 and 14.9 Hz) 128.9 128.9
6.31 (1H, dd, 11.0 and 11.0 Hz) 6.31 (1H, apt, 11.3 Hz) 130.4 130.4
6.61 (1H, d, 16.0 Hz) 6.62 (1H, d, 15.9 Hz) 134.0 134.0
6.83 (1H, s) 6.84 (1H, brs) 140.5 140.51
7.31 (1H, s) 7.33 (1H, brs) - 140.56
7.40 (1H, dd, 11.0 and 15.0 Hz) 7.39 (1H, m) 144.6 144.6
7.40 (1H, m) 7.41 (3H, m) 166.0 166.1
7.41 (2H, m) - 167.4 167.5
7.65 (1H, d, 16.0 Hz) 7.66 (1H, d, 16.0 Hz) -
-7.71 (2H, m) 7.72 (2H, m) -
-1. Barsby, T.; Kelly, M. T.; Andersen R. J.; J. Nat. Prod. 2002, 65, 1447; Kelly, M. T.; Anderson, R. J.; Barsby, T.; US Patent 2005/0277779 A1, 2005.
