The absolute configurations of halogenated chamigrene derivatives from the marine alga, laurencia glandulifera kützing

CONF’IGURATIONSOF HAuxiENATED

CHAMGRENE DERIVATIVES FROM THE MARINE ALGA, LALmENcLA GLAND-G’

Maoy batopenotedclJmigreoc dcrivalivcs have bao isolakdfromtbemarhw (Rbodomelscere;Bhodophyta).z-In Ihe cmlmc of oar ccmthwd saw3ies of cJum@m dtzhtivm, we have repo?ed& strucmaof fourcbunioreadypebfonmsesqunapeaes,isolatedfromL~em~10 -bmmo-3,4-qxxy-a-cbunipnae(l),~~ (2),10-bromo-a-c~-4-ooe(3)andl0bmlo-~-chmigml-4-ooe.7**~,aa CXtthVCStUdyOftlkCllydlWhOllpUtOfthClk?&Sl L?ssehloiloftbiaJgakdtotbeisolatimof4,10dibromo-3-chloro-a-~(1)andlO-komoa-chsmilgeac(~,prcviouslyisdatedfromL~ altdLspcck,~titbe(3utlofcatif~ WelweehicidaMtheabsolutc~of1,t3, 4andSbyX-raydi5achamlysismdtkc9mical mealods.neprcseatpapcr~tbeiso~tbe structurcsalldthe~~oftbesehelogeaated chamigrcm in derail.

v--

Stnwtun of IO-bnnno-3.4-rpaxys-~~n?ne (1,” 1~Bmal*3,4epoxy-Q-c~, c,rHsoBr, (AI+ 300 and 2!98),m.p. 53-w, [U]D- w, shows no OH nor

4

5 AC 1. a23

6

hgkcryatalwitbdimat8hofabo4tto.4xo.4xo3mm wa8udforthex-ray ~t.ccll~ andredectiw~wm~uredona~u folIr&~~QlKondhtioo(A= 1.54178AIm witb a iip crystal. The

Table 1. ‘~NMR~of 6

li!ultiplicity

141.6

C-7

119.2 61.9 58.7 55.5 43.0 42.5

: : s s 9

35.7 29.4 27.8

t t t

26. s 25.4 22.3

t-l

20.6 17.9

I Assignment

Cc::0 ::j C-6 and 11 C-l,

2,

5.

atid 9

c-14 c-15

: 9 Q

C-12’ and 13

hladcrtoeh&iatctheatNcturcofl~tbc abwh&Mntkmrrk*l.aaiagkuystalof1wa8* jcctcdto X-raydiihdon analysis. CMorkss,phtdikc crystals of 1 were obtained by cdugahotmethawtdutioatoroomtemperature.A

m/c 133

m/e 175 !schu

BR

1.

m/c

218

(8) ~ydrorpa -_--_-.-__-_ AtOm -_. -

atolm

.---------

x __._ -. -1776(l)

Br

Y

-..--.--

-._-_

2

1878(l)

201(l)

-153(4)

7299(6)

0

1225(r)

C(1)

-363(S)

874(4)

C(2)

-759(S)

16(6)

611

-. .-_.-_--

103(l)

611

75(3)

68(O) 66(Z)

683 270(l)

16(l)

163(7)

623

611

612

-11(S)

-73(2)

66(l)

-57(E)

-20(7) -20(O)

50(10)

.5615(E)

730)

4w

1X(9)

6396(g)

64(4)

71(4)

161(g)

-32(6)

6791(g)

79(4)

55(3)

167(g)

-29(a)

-26(11)

12(9)

-3(S)

18(S)

22 (10)

4(10)

195(6)

-607(S)

C(4)

1168(S)

-S81(4)

5651(a)

69(4)

44(2)

179(10)

-44(10)

-18(E)

C(5)

1173(4)

-26(r)

4095(8)

56(3)

39(2)

169(E)

6(4)

17(9)

-18(7)

C(6)

432(4)

827(3)

4064(7)

55(3)

32(21

148(7)

l(4)

13(8)

-29(a)

C(7)

1215(S)

16370)

4199(9)

68(4)

40(2)

196(10)

-17(S)

ll(10)

-S2(8)

C(8)

lOSl(8)

2361(S)

3313(14)

112 (6)

37(21

306(17)

-41(7)

-6(17)

-19(11)

2493(S)

2039(14)

136(a)

39(2)

309(19)

-21(7)

-37(21)

1771(4)

2146(g)

830)

41m

202(10)

2319(7)

56(3)

35(2)

165 (8)

684(S)

841(9)

81(4)

65(3)

153(9)

147(4)

2290(10)

75(4)

48(3)

2lS(ll)

1609(6)

5456(12)

98(S)

64 (3)

237(l))

-47(7)

-40(l))

7776(12)

138(E)

74(4)

201(14)

-Sl(lO)

Atom

x

C(3)

14S(9)

C(9) cc101

-725(6)

cc111

-219(4)

8S3( 3)

S90(6)

C(I2)

-1153(6)

C(l3) CC141

2148(7)

C(lS)

-83(10)

\ttm

x

II( I:11

-1411(7)

Y

-lob(g)

Il(lb)

2(9)

B

7.

9(S)

28(12) 6(8)

8(llI -7(9)

-21(7)

la(6)

lO(11)

-3S(9)

-27(6)

-64(12)

-6(4)

Y

3(9) -S6(12) 36(13)

8(18)

B

2

120(7)

S29(16)

6(2)

H(12b)

137(O)

114(7)

102(1S)

6(2)

119(7)

634(14)

5(2)

H(12c)

30(9)

86(7)

39(1S)

6(2)

Il(?O)

-128(6)

-34(S)

581(10)

3(l)

H(13a)

-109(9)

Il(tb)

-12S(ll)

lS(8)

744(17)

7(t)

H(l3b)

-159(9)

H(4)

lSS(9)

-126(7)

525(X)

6(2)

H(13c)

-156(11)

14(8)

290(17)

7(2)

304(10)

4(l)

H(14a)

201(9)

155(7)

616(14)

6(2)

H(Sa)

73(6)

H(Sb)

189(8)

H(8)

148(9)

-46(S)

-33(14)

H(9b) H(10)

-108(g)

H(12a)

1’*3. C(l)-C(2)

18(7)

238(14)

5(2)

83(14)

S(2)

383(11)

4~21

H(l4b)

242 (10)

210(E)

532(17)

70)

290(7)

339(14)

6(2)

H(14c)

263(g)

llS(7)

Sll(l6)

6(2)

241(9)

113(18)

7r31

SlO(l2)

213(23)

189(7)

29S(lS)

14(61

40(12)

H(h)

-54(7)

70(7)

8(6)

H(15a)

67(15)

-178(13)

801(24)

lO(4)

lO(4)

H(lSb)

-66(12)

-171(10)

724(20)

8(3)

S(2)

H(lSc)

-3S(8)

-129(a)

848(13)

S(2)

88(12)

4(2)

-

B~~(A)Imd~(det):kut-rqtrucrcrtimrtcd~dnhtionruclinaia-tbaec 1.520(10)

C(2)-C(l)-C(6)

118.215)

C(6)-C(7)-C(I4)

--118.0(6)

C(l)-C(6)

1.556(8)

C(l)-C(2)-C(3)

113.1(S)

C(8)-C(7)-C(14)

119.4(7)

C(2)-C(3)

1.508(10)

C(2)-C(3)-C(4)

116.3(6)

C(7)-C(8)-C(9)

12S.S(7)

C(3) -C(4)

1.468(s)

C(Z)-C(3)-C(lS)

117.3(7)

C(8)-C(9)-C(10)

110.9(7)

C(S)-C(l5)

1.489(13)

C(t)-C(s)-0

112.8(a)

C(9J-c(1o)-c(l1)

113.716)

C(3) -0

1.462(g)

C(4)-C(S)-C(15)

121. S(7)

C(9)-C(lO)-Br

108.9(6)

C(4)-C(5)

1.499(9)

C(4)-C(3)-n

60.1(4)

C(ll)-C(lO)-Br

113.0(4)

CO)-0

1.466(8)

c(ls)-c(3)-o

115.3(7)

C(6)-C(ll)-C(l0)

107.0(S)

C(5)-C(6)

1.567(7)

C(S)-C(4)-C(5)

122.0(S)

C(6)-C(ll)-C(l2)

111.2(4)

C(6)-C(7)

1.547(8)

c(3)-c(4)-0

C(6)-C(ll)-C(13)

110.1(S)

C(6)-C(l1)

1.590(S)

C(5) -C(4)

119.3(5]

C(1o)-c(l1)-c(12)

109.3(S)

C(7)-C(8)

1.322(10)

C(4)-C(S)-C(6)

118.5(S)

c(lo)-c(11)-c(13)

110.7(S)

C(7)-C(14)

1.493(11)

C(l)-C(6)-C(5)

111.50)

C(12)-C(ll)-C(13)

108.6(S)

59.7(4) -0

C(8)-C(9)

1.492(15)

C(l)-C(6)-C(7)

lOS.S(S)

C(9)-C(10)

1.509(11)

C(l)-C(6)-C(l1)

113.50)

C(lO)-C(11)

1.526(8)

C(S)-C(6)-C(7)

108.7(4)

C(lO)-Br

1.994(7)

C(S)-C(6)-C(11)

107.9(4)

C(ll)-C(12)

1.540(9)

C(7)-C(6)-C(11)

109.40)

C(ll)-C(l3)

l-543(8)

C(6)-C(7)-C(8)

122.6(6)

826

Y. Buxalxlud

‘lhresnltaarcgiveniaTabksUamlPi&2.’fbcH atamsarcdewtedbytheaumbcroftheCatomtowhich theyarcattackd,su5xedbya,b,c,whaencccuuy. lbealwIopkauiirotropictkrm8lpsnmetenam

hvk!wof’~NMRstudyrtudy8bkshtlled.rwtwcof2 walddbertzpMedas10-bmtDo-4-chlofo-3Iiydroxy-o-cbam&lcaaditw8llddtnitelycoafirmed bythetrc&wtof2withpotawhhydroxitk. T&b%‘~NWtstmdmmof2 6

Wltiplicity

139.9 122.0 71.9 66.1 61.2

:

Assignment

ti~distancesaod~arcallwahinthe Ob&?IVCdrrrqle.‘0l%CcyclobexesreriDgtaLec~-

qlo) and cxll) atom8 lyhg0259aad0J18rj,rboveandbl?lowtllebl!8tplaac tluoughtkq6),co,~andco~;~~,q5) awl q13) atomsan eqaataially or p=VdY bdkhif

Cd-

with t&e

bomkdtotlli8riug.onthcotkrheod,thecyclohelurae

rhgldoptsa8omewhatMenfx$twist-boatcaaformathlwitilanfgpro~two-foldrotatiollaxisnmn&thlghtbemiddlcpohtsoftbeql~aDd q4)-q5)bonds.Thecpoxyoatomisverycbxetothe ql)atoQl&rdistance~279o~

: d

::; c-3 c-4 c-10

48.1 42.7

S

E:L

36.2 35.9

t

31.6 39.1 25.8 24.7 22.1 17.3

t t

t

C-l, 2, 5, and 9

I

: q 9

c-14 c-1s C-12 and 13

C(6)-C(l)-C(2)-C(3)

51.6

C(l)-cc-)-C(3)-CO)

-32.8

C(ll)-C(6)-C(7)-C(14)

C(l)-C(2)-C(S)-C(lS)

171.6

C(l)-C(6)-C(ll)-C(l0)

68.1

33.9

C(S)-C(6)-C(ll)-C(l0)

-167.8

C(l)-C(2)-C(S)-0 C(2)-C(3)-C(4)-C(S)

C(ll)-C(6)-C(7)-C(8)

21.9 -161.6

-5.3

C(7)-C(C)-C(~ll-C(lO1

-49.7

c(ls)-c(3)-c(4l-c(s) o-c(3)-c(4)-c(s)

149.3 -107.7

C(7)-C(6)-C(ll)-C(l2) C(7)-C(6l-C(ll~-C(lS)

-170.0

C(2)-C(S)-O-C(4)

-108.3

C(6)-C(7)-C(ll)-C(9l

-2. S

113.2

C(l4)-C(7)-C(S)-C(9)

-178.9

27.6

C(7)-C(8)-C(9)-C(l0)

c(ls)-c(3)-o-c(4) C(3)-C(4)-C(S)-C(6) 0-C(4)-C(S)-C(6)

-43.1

C(8)-C(9)-C(lO)-C(l1)

c(s)-c(4)-o-c(3)

112.1

C(8)-C(9)-C(lO)-Br

C(4)-C(S)-C(6)-C(1) C(4)-C(S)-C(6)-C(7) C(4)-C(S)-C(6)-C(11) C(l)-C(6)-C[7)-C(8) C(S)-C(6)-C(7)-C(8)

-9.4

h9.6

12.4 -44.4 -171.3

C(9)-C(lO)-C(ll)-C(6)

64.2

'106.8

c(9)-c(lo)-c(11)-c(l.)

-56.3

-134.7 -100.7

c(9)-c(lo)-c(11)-c(13) 8r-c(lo~-c(ll)-c(6)

-175.9 -171.1

139.5

The absolute configurations of halogenated chamigrene derivatives from the marine alga. L. lI{afldu{i!era Kutzing

The mild treatment of 2 with 5% methanolic potassium hydroxide gave a dehydrochlorination product, C. S H2 30 Br, which was identical with 10 - bromo - 3,4 epoxy - a - chamigrene (I) by the mixed m.p. and by a comparison of the IR and PMR spectra and the optical rotation with those of an authentic specimen. This easy epoxide formation suggests that the vicinal a and OH groups should be trans as shown in Fig. I and easily become in the situation of anti-relationship each other, when they do react. On the consideration of ring conformation of 2, the pMR spectrum has given the information. The PMR spectrum of 2 showed the chloromethine proton at 4.67 (dd, J = 9.5, 9.5), coupling with the adjacent methylene protons. This coupling constant are consistent with the twist ring form, in which the dihedral angie between the chloromethine proton at C-4 and one of the adjacent methylene protons at C-5 is very small and that between the proton at C-4 and the other of methylene protons is around 140°." In an attempt to clarify the configuration of the a and the OH groups and the ring conformation of B-ring, we studied the PMR spectrum of 2 in the presence of shift reagent, Eutfod), (Tables 6 and 7). The shift reagent studies indicate that the stereochemistry of the a is equatorial since the chloromethine proton clearly gives the typical coupling constant for axial H (dd, J = 12.0, 5.0). In addition, the equatorial nature of the OH group is indicated by the less induced shifts for the axial protons at C-I and C-5 than those at C-2and C-4and also by the equal inducedshifts for both axial and equatorial protons at C-1 and C_5. 12 The stereochemistry of B-ring in 2 is now shown provisionally as the formula 7 (Fig. 3). The alternative formula 8 seems to be energetically unfavorable, since one Me group of gem-dimethyl group at C-II has equatorial configuration and thus non-bonded interaction of the equatorial Me group at C-II to the a at C-4 are recognized on the Dreiding model. On the other hand, it is apparent that the shape of B-ring in formula 7 fun-

damentally changes in twist boat form to relieve the interaction between the Me group at C-7 and two axial hydrogens at C-2 and C-4. Formula 9, which possess the twist boat form for B-ring, is now proposed for glanduliferol (2), decreasing the interaction between the Me group at (-7 and two axial hydrogens at C-2 and C-4in 7 and permitting the coupling constant (J = 9.5,9.5) for the chloromethine proton at C-4 coupled to the adjacent methylene group at C-5. From these considerations, it is assumed that the conformation of B-ring in 2 changes to normal chair form from twist-boat form during the addition of shift reagent of Eu(fodh, because of newly generated non-bonded interaction of Eutfodl--cornplex, and thus the change of coupling constant of the chloromethine proton, J = 9.5,9.5-> 12.0, 5.0 (on addition of the shift reagent), is smoothly explained. Moreover, in the PMR spectrum of 2, the signal of the olefinic Me at C-7 appears in considerably low field compared with those of the other compounds, I, 3 and 5 (Table8). This down field shift is easily explicable by the reason that the olefinic Me at C-7 is in the situation closed to the OH group in formula 9. This assumption is supported by the hydrogenation of 2 with Pt0 2 yielding the dihydro compound (10). In the PMR spectrum of 10, the coupling constant (dd, J = 11.0, 5.0) of the chloromethine proton at C-4 reveals that the CI has an equatorial orientation and the change of coupling constant (9.5, 9.5 on 2-> 11.0, 5.0 on 10) seems to be caused by the change of B-ring conformation from twist boat form (formula 9) to normal chair form (formula to) which should be accompanied by the change of A-ring shape from slightly distorted chair form to normal chair form during the hydrogenation of 2, and disappearance of one of the two interactions betweenthe Me groupat (-7 and two hydrogens at (-2 and (-4 in 7.

Structure of IO-bromo-a-chamigren-4-one (3)'" 100Bromo-a-chamigren-4-one, C.S H2 3 0 Br, (M+ 300 and 298), m.p. 78-7~, [a]o-88°, showed the presence of

Table 6. Spin decoupling results in the PMR spectra of 2 in CCI. after the addition of 0.5 molar equivalents of Eu(fodj, Run

Proton

()

Multiplicity change

Irradiated

la

C:..-H

2a

C-H(ax) )

13.74

6.1 c

Obse rved

•

4a

CS,H(eq)

C

2·H(ax)

S.07

CS,H(eq)

S.07

dd(J=14.S) - d(J-14)

10.90

b

C 4·H

C

6a

C

2·H(eq)

9.80

1·H(ax)

dd(J-12. S) .. b r

5

12

br

5

14

S.07

dd(J-14,S)

13.74

dd(J-12,S)

-+

• d(J'12)

6.1S

dd(J-14,12) - br d(J-12)

C 2·H(eq)

9.80

br d(J-14)

l·lI(ax)

C 2·H(ax) Cl·H(ax)

-S.4

13.74

CS,H(ax)

C

Sa

t i

ddt')

dd (J=14 .12)

CS·H(eq) 3a

~

6.1S

4·H

Sp l it

ng

dccoupled (liz)

CS·H( ax)

C

-S.4 10.90 _S.4

C 2·H(ax)

10.90

C 2,H(eq)

9.80

X2i

-+

br

5

14 14

ch br t(lI

l1

33) • dd(J-12,4)

14

ch br t(l'H 33) - m(II 24) H br d(J-14,II

Abbreviations; "s": singlet, lid": doublet, "til:

"m": multiplet, "ch'": change,

H

24) - br d(J=14'\,'H

~O)

triplet, "dd'": double doub l e

"o r":

broad

t ,

etl(C.w,

0

0.25 ml*

Cmtm

b

6

cl-q(a)

A0.25

61.0 Ku

-5.k

-3.5 t -3.8

-7.3

-5.4

-2.9

-1.0 1 -1.3

-3.1)

-1.9

-5.1

-3.2 t -3.5

-d.7

t

-2.2 lO.90

-4.4

1

-4.7

c3-q3

6

-1.6 1 -2;1

6.30

c2-‘2!w

4;s

-3.7

1.9 C2qga)

6

6u

1.6

Cl-‘2!(.9)

1.0 vh

0.5 mh

5.20. -3.9 1 -4.2

9.aO

2.36

b.74

-2.54

7.95

-9.0 t -9.3

14.60

-7.9

16.20

-12.7

I

-13.0 -14.3

t

1

-14.6

-u.2 -5.65

11.40

-9.10

C,-‘?!

4.67

9.32

-4.65

13.74

-9.07

28.68

-14.01

c,-q(a)

2.20

4.21

-2.01

6:15

-3.95

8.19

-5.99

Cp?$nl)

2.20

-1.5

5107

-2.87

6.65

-4.45

-l.79

4.79

-2.75

-0.62

6.10

-0.90

-3.7

Cp?!,

2.00

2.92

-0.92

3.79

Cp?!

5.20

5.51

-0.31

5.82

-2.5

c9-% %o-= cl,-c3(=)

Ao’25 Bu

I

6

-0.7

-3.5

-1.0

-0.54

5.55

-1.08

6.10

-1.53

0.96

1.62

-0.66

2.23

-1.27.

2.94

-l.98

-1.67

3.82

-2.66

-60.25 cc14

7

-3.2

-0.3

5.01

1.22

Clp?!,(W

-2.a

4.47

2.07

lu(fod)2’

-0.85

Aoe5.6 Lu

2.69

-60.5

Ccl4 Cu(fod)2*

9

J.

0.93,

x.10

l.?Cfbtrf

4.32fdd.3-8.wLD

I

O.%, 1.22

i?.W[brtf

b*4?fdd,J=lo0.0.3.0

If*> Ii*

4.bXddrJ3r4.P.S Btf

3

o.u7. 1.20

LfS(br s)

4.53(dd.J-S.7.8.3 Br)

I

0.95. 1.22

c&Z.O(br

4.42tdd.J.10.0.7.0 Ilr)

iI

0.92, 1.10

Lb4cbt 8)

4.bP(dd,J-S.O,?.S itd

E

LO?. Lx6

I.tSfd,J*7.0II3

4,15tdd,J-l2*O,LPart

4.23Wd,P11,@,3.O Its1

P

1.07r I.&i

t,2l[d,J-7.0R3

4.2lfdd,J-l2.0*kO&I

4.291dd,J-13.0,C.O iirZ

a)

4.78UdrJrll.3,U.IS Us)

M. SUZUKI et al.

X10

Sr

~H Ie)

j

CI

(a)

..

~ .

~

(h)

I

''0

2

Sr

~'

..

~., 0

~

~

~

3

Sr ...

(c)

~

6

Sr

5

(c)

Sr

Sr

Zn - dus t/CfI

4

3COOH

Sr~...sr

~r

13

14

15

Scheme 3.

Isolation. Air dried seaweed (8.5kg) was extracted with MeOH and the neutral essential oil (90g) was extensively chrornatographed over neutral alumina. The n-hexane fraction was rechromatographed over silicic acid with a-hexane. The earlier fraction consisted of S,u laurene and isolaurene.' and successively eluted fractions contained a-bromocuparene and o-isobromocuparene." Later fractions consisted of 4'< and bromoethers." Each fraction was repeatedly chromatographed on a silicic acid column and on preparative silica gel plates to yield S (70mg,0.0008% dry weight alga) and 4 (ISO mg,0.0018%). The n-hexane-benzene (10:I) fractions were chromatographed on silicic acid. From the earlier benzene eluates, crystalline compounds were obtained and the successively eluted fractions gave pure spirolaurenone" (1.2 g, 0.014%) as a colorless oil. The crystals were cautiously recrystallized from MeOH to give I (SO mg, 0.0006%) and 3 (SO mg, 0.0006%) and 10 - bromo - /3 chamigren - 4 - one" (100 mg. 0.0012%). The ether fractions consistedof an alcoholic mixtureand this mixturewas acetylated with Ac20 in pyridine. The acetylated mixture was chromatographed over silicic acid to yield pure 2 (800 mg, 0.009%) along with laurencin" and cholesteryl acetate. IO-Bromo-3,4-tpoxy-a-chamigrtnt (I); m.p. 53-54° (from MeOH); [aID-9ZO (c, 0.98); UV, A~~H only end absorption;IR, v~~) 1660, 1390, 1372, 1183, 1160, 1130, 1110, 1053, 1033, 965 and 830em~ ': mass, mit (relative abundance) 300 and 298 (M+, 3).219 (19),218(40), 200 (38),185 (41),175(19),159(38),157 (44), 135 (54), 133 (74), 119 (100), 105 (74), 91 (65), n (43),69 (51)and 55 (65). (Found: C. 60.09; H, 7.88. ClsHnOBr requires: C,60.23; H,7.74%). Glanduliftrol (2); colorless gum; [aID- 21.7" (c, 1.66); IR, v~~?) 3580, 1655, 1400, 1390, 1342, 1130, 1105, 1070, 1045,990,

980,928and 832em~'; mass, mit 336, 334(M+, 0.1),300, 298 (I), 219(38), 218 (15), 201 (31), 185 (15), 175 (36), 159 (56), 149 (100), 133 (77), 119 (92), 105 (87), 91 (82),77 (49),69 (51) and 55(SO). 100Bromo-a-chamigrtn-4-ont (3); m.p. 78-79" (from MeOHH20 ); [aID-88° (c, 2.46); UV, A;~~H 284nm (E 30); IR, V~~~OI 1695, 1183, 1033, 892, 844, 818 and 795cm- I , v~~, 1703, 1395, 1380, 1183,890,840 and 810cm~l; mass, mit 300,298 (M', 23), 243, 241 (6), 219 (100), 218 (22), 201 (42), In (SO), 175 (14), 164 (56), 147 (56), 135 (45), 133 (45), 119 (46), 105 (55), 91 (33),77(42), 69 (89) and 55 (54). (Found: C, 60.08; H, 7.83). 4,IO-Dibromo-3-chloro-a-chamigrtnt (4); colorless oil; [aID14° (c, 1.45); IR, ,,~. 1389, 1081, 1051, 991, 975, 837, 818 and 790em~ I; PMR, a 0.95 (3H, S), 1.22 (3 H, s), 1.66 (3 H, s), ea 2.0 (3 H. br. s), 4.42 (I H. dd. J = 10.0 and 7.0 Hz), 4.78 (I H. dd, J = 8.5 and 8.5 Hz) and 5.2(I H, m); mass, mit 402,400, 398, 396 (M', 15), 321, 319, 317 (32), 283, 281 (3),201 (34), 159 (45), 145 (100), 133 (40), 119 (95), 109 (SO) and 91 (89). IO-Bromo-a-chamigrent (5); colorless oil; [aID- 81° (c, 0.92); IR, ,,:::: 1399, 1389, 1379, 1190, 1074, 847, 817 and 790cm~l; PMR, a 0.92(3 H, S), 1.10 (3 H, s), 1.64 (6H, br. s), 4.64 (I H, dd, J = 9.0 and 7.5 Hz), 5.18 (I H, m) and 5.38 (I H, m); mass, mit 284, 282 (M+, 7), 216, 214 (48), 203 (II), 202 (7), 135 (100), 119 (42), 109(24)and 91 (25). Treatment of I with 1M ethanolie KOH. A solnof I (16mg) in 1M etbanoli<: KOH (2 mI) was refluxed for 30min in a streamof N2. After being cooled, the mixture was extracted with ether. The ethereal soln was washedwith water and dried over Na2SO•. After evaporation of the solvent, the residual oily material was chromatographed on silicic acid to give a conjugated cyclehexadiene (5mg) as a colorless oil; [aID+ 1100 (c, 0.95); UV, A~H 264nm (E 29(0); IR, ,,~~;'l 1603, 1385, 1362, 1100, 1051,

The absolute configurations of halogenated chamigrene derivatives from the marine alga. L glondulijeru Kutzing

M31

1031. 1007.990.965.918,888 and 840cm-': PMR. s 0.96(3 H. s), 1400,1390, 1100,990.969,867 and 852cm '; PMR, s 1.07 (3 H. 1.09 (3 H. s), 1.22 (3 H, s), 1.70 (3 H, br. s), 2.79 (I H, d, J = s), 1.16 (3 H, s), 1.21 (3 H. d, J = 7.0Hz), 1.68 (3 H. s), 4.21 (I H. 4.0 Hz), 5.0-5.7 (3 H, m): mass, mle 218 (M+, 29), 203 (17), 200 dd, J = 12.0 and 5.0Hz) and 4.29 (I H. dd, J = 13.0 and 4.0Hz): (10), 185 (16), 175 (25), 159 (44), 157 (36), 133 (73), 119 (100), 105 mass; mle 402, 400and 398 (M+). (91),91 (77),77 (52), 69 (35) and 55 (63). Treatment of 1 with boron trifluoride etherate. A soln of 1 REFERENCES (32 mg) in benzene (0.5ml) was treated with BF,-Et~O (0.2ml) at room temp. After 5 min, water was added and the mixture was 'Part XXX: Constituents of Marine Plants. Part XXIX: M. extracted with ether. The ethereal soln was washed with water Suzuki and E. Kurosawa, Tetrahedron Leiters 2503 (1978). and dried over Na~SO•. After evaporation of the solvent, the 2o J. J. Sims, W. Fenical, R. M. Wing and P. Radlick, 1. Am. Chem. Soc. 93, 3774 (1971); •J. J. Sims, W. Fenical, R. M. Wing residue was chrornatographed over silicic acid to yield crystals of 3 (20mg); m.p. 76-77° (from MeOH); [alo-9O" (c, 0.59); the IR and P. Radlick, Ibid. 95. 972 (1973): -n 1. Faulkner. M. O. and PMR spectra were superimposable upon those of natural Stallard and C. Ireland, Tetrahedron Letters 3571 (1974); d 1. 1. compound 3. Sims, W. Fenical, R. M. Wing and P. Radlick, Ibid. 195 (1972). Treatment of 2 with 5% methanolic KOH. A soln of 2 (55mg) 30S. M. Waraszkiewicz and K. L. Erickson, Ibid. 2003 (1974): ·S. M. Waraszkiewicz and K. L. Erickson. Ibid. 281 (\975): 'S. in 5% methanolic KOH (3ml) was allowed to stand at room M. Waraszkiewicz and K. L. Erickson, Ibid. 1443 (1976), -s. M. temp. for 7 min. After being treated in the usual manner, the products were chromatographed on silicic acid to give crystals of Waraszkiewicz, K. L. Erickson, 1. Finer and 1. Qardy, Ibid. 1 (22 mg); m.p. 52-53° (from MeOH); [alo -7~ (c, 0.96»; the IR 2311 (1977). and PMR spectra were superimposable upon those of natural I. 'J. A. McMillan, I. C. Paul, R. H. White and L. P. Hager, Ibid. Hydrogenation of 2. The hydrogenation of 2 (30mg) was 2039 (1974). 'J. J. Sims, G. H. Y. Lin and R. M. Wing, Ibid. 3487 (1974). performed in EtOH over PtOrcatalyst. After removal of the .0A. G. Gonzalez, 1. Darias, A. Diaz, J. D. Fourneron, J. D. catalyst and the solvent, the residual oil was chromatographed on silicic acid to give 10 (16mg) as a colorless oil; [a 10 + W (c, Martin and C. Perez, Ibid. 3051 (1976); • A. G. Gonzalez, J. D. 0.78): IR, II~~,CI, 3600, 1390, 1343, 1315, 1100, 1080, 1017,990. Martin, V. S. Martin, M. Norte, J. Fayos and M. M.-Ripoll, Ibid. 2035 (1978). 987,930,890,866,854 and 835 cm-': PMR, /j 1.07 (3 H, 5),1.16 (3 H, s), 1.19 (3 H, d, J = 7.0 Hz), 1.29 (3 H, s), 4.15 (I H, dd, 'OM. Suzuki, E. Kurosawa and T. Irie, Ibid. 821 (1974); "M. J = 12.0 and 5.0Hz) and 4.23 (I H, dd, J = 11.0 and 5.0Hz); mass, Suzuki, E. Kurosawa and 1. Irie, Ibid. 1807 (1974); -a M. Howard and W. Fenical, Ibid. 1687 (1975); -s. M. Howard and mle 338 and 336(M+). Treatment of 2 with zinc-dust-acetic acid. To a soln of 2 W. Fenical, Ibid. 2519 (1976); 'T. Suzuki, A. Furusaki, N. (61 mg) in AcOH (5 ml) was added Zn-dust (150 mg), and the Hashiba and E. Kurosawa, Ibid. 3731 (1977). ·W. C. Hamilton, Acta Crystallogr. 18,502 (1965). mixture was stirred for 3 hr at 60° (bath temp). After cooling and "lntemationo! Tables for X -ravCrystallography, Vol. IV, pp. 71. filtrating off Zn-dust, the mixture was extracted with ether. The The Kynoch Press, Birmingham, England (1974). ethereal soln was washed with water, 5%-NaHC03aq and finally with water, dried over Na2S0., and evaporated. The residual oil ,oMolecular Structures and Dimensions, Vol. Al (Edited by O. was chromatographed on silica gel plates with n-hexane to give 6 Kennard, D. C. Watson. F. H. Allen, N. W. Isaacs, W. D. S. (8 rng) and 5 (4 mg) (28 rng of 2 was recovered): 6, colorless oil, Motherwell, R. C. Pettersen and W. G. Town), the International Union of Crystallography and the Crystallographic Data CenC"H 2• imle 204; M+), [alo - 30" (c, 0.36); the IR and PMR spectra were identical with those of o-chamigrene: 5, colorless ter, Cambridge, England (1972). oil, [alo-92° (c, 0.39); the IR and PMR spectra were superim- "N. S. Bhacca and D. H. Williams. Application of NMR Specposable upon those of natural 10 . bromo - a - chamigrene (5). troscopy in Organic Chemistry. Holden-Day. San Francisco (1964). Treatment of 4 with zinc-dust-acetic acid. To a soln of 4 (29mg) in AcOH (2 ml) was added Zn-dust (100mg), and the '2p. V. Demarco, 1. K. Elzey, R. B. Lewis and E. Wenkert, 1. Am. Chem. Soc. 92, 5734 (1970). mixture was stirred for 2.5hr at 50" (bath temp). After cooling and filtrating off Zn-dust, the mixture was extracted with ether. "Y. Ohta and Y. Hirose, Tetrahedron Letters 2483 (1968). The ethereal soln was washed with water, 5%-NaHC03aq and ''T. lrie, T. Suzuki, Y. Yasunari, E. Kurosawaand T. Masamune, Tetrahedron 25,495 (1969). finally with water, dried over Na2S0., and evaporated. The residual oil was chromatographed on silica gel plates with n- "T. Suzuki, M. Suzuki and E. Kurosawa, Tetrahedron Letters 3057 (1975). hexane to yield5 (7 mg)(10mg of 4 was recovered), colorless oil, '6M. Suzuki and E. Kurosawa, Ibid. 4817 (1976). [a lo - 110° (c, 0.48); the IR and PMR spectra were superimpos170M. Suzuki. E. Kurosawa and T. lrie, Ibid. 4995 (l970); "The able upon those of natural 5. full details of the structure and stereochemistry of Hydrogenation of 4. The hydrogenation of 4 (35mg) was spirolaurenone will be reported in the near future. performed in EtOH over Pt0 2-catalyst. After removal of the catalyst and the solvent, the residual oil was chromatographed 'sr. Irie, M. Suzuki and T. Masamune, Tetrahedron 24, 4193 (1968). over silicic acid to yield 13 (19mg); [aJo+4r (c, 1.4); IR, 1I~~,C1,