Polysiphenol, a new brominated 9,10-dihydrophenanthrene from the senegalese red alga polysyphonia ferulacea

TcmhcdronLetters, Vol 33,No 4 pp 555558,1992 Prlntcd UIGrcm Br~tam

0040.4039/92 S3 00~ 00 PergamonPress plc

Polysiphenol, a New Brominated 9,10-Dihydrophenanthrene from the Senegalese Red Alga Polysyphonia ferulacea

MaunLe AKNIN, Departement de Chlmle

Abdouldye SAME Chctkh Anta Dlop dc Dakar, Senegal

Untventtc

Joseph MIRAILLES Departement de Bmlogte Vegetalc, Umvcrw~ Chclkh Anna Dlop de Ddkar Scnegdl

Vdlena COSTANTINO, Ernesro FATTORLSSO,* and Alfonso MANGONI Dlpartlmento dl Chlmlca delle Sostanze Naturah, Untver~tra deglt Studt dt Napoh Federtco II, wa D Montesano 40, I-X0131 Napnh, Ik4y

Key Wards 9 l@dlhydrophenanuene

dcrtvattve

brnmophenol

dertvdtwi,

Poiystphoosn fcrulacea

Absl*aet Polysphenol (3), the ftrst met&4te wtlh d 9 lO-dth~droplren,trlthrcne qkclrton twldltd from the Senegale\e red alga Pnlpciphonia frrulrrl PC! Ir$ \tructttrc, mcludmp dbwluts wnftguwtlon, data, and 1IsCOnfOrmaltOn studted by nlok5LUldr meLhdllK5

Asapartofourcontmumg

mvebtlgatlonb of marme ndturdl ploduLt\from

theredalgaPo[yslphonrafevulurea some bromophenol

(Rhodomeldcede,

Rhodophyceae)

the Senegdlesecoait,

Lompounds’ 3 which dre common to several Rhodomelaceae

SpeCltWnS

(3), which to our knowledge of P

with MeOWCHCl,

(2 1) dnd the crude extrdLt (1 35 g)

solvents ofmcreasmg

polarity

CO~UITZI (n-hexdne-ethyl

Wd5

species 4

tn July 1990 Fresh nlgae were extracted

I&k(u)

subrmtted to sihca gel ~olutnn chromatography

acetate 1 1) to give pule compound5

reported 5h Compound

by SLheuer

S-dlhydroxybenzyl

as d methanol

extractlon

alcohol (2) have aftlfact

9

10

E3r

H

H Br

HO OH 1

R = CH,

2

R = H

HO

with

by HPLC on dn SQ ‘. Merck

1 (3 1 mg), 2 (2 I mg) and 3 (19 mg)

metyl ether (1) dnd 2 %dibromo-4 1 wds considered

Lompound,

Isolated from maIlne organisms

A fraLrlon eluted with benzene was Lhromntographed

2,3-dlbromo-4,5-dlhydroxybenzyl been previously

\ottth

we have studled

of d new bromophenol

15the tu-\t 9 10 dlhydrophennnthrene

ferduceu were Lollected dt Jodl (100 km

from mdrtnC ?OtITCCWdb Isolated ws, deterrnmed by Spcctro~coPL

The genusPol> qhorz~~ 15known tocontam

The present paper deal5 wnh the lsoldtlon dnd strut rural determmatlon polyslphenol

red algae, tnolectllar meLhanlcs

Br

Br

3

OH

7

556

Table 1. NMR Spectral Data for Compound 3 Pos

6, (mult)

1-8 2-7 3-6 4-5 4a-4b 10-9

Detected C-H couphngs

i?iCimult)

6 84 (s)

113 5 (CH) 143 2 (C, 1392 (C) 110 1 (C) 127 0 (C) 31 2 (CH,)

ax 2 SOb eq 2 tXIh

1Oa-Xa

tn HZ)

Hl-8 (156 8 ), H,lO-9” Hl-8 (3 4), H,lR-9” Hl-8 (7 6) Hl-8 (1 7) Hl-8 (7 9), H,lO-9 (7 4,7 4) Hl-ga, H,10-9 (131 2)

135 59 (C)

H,lO-9 (6 5’)

’ Carbon srgnal sharpened by Irrddtatjon, but Louplrngconstant could not be evaluated ‘The couphng constant refen onl) to one of the methylene protons the other Lonstmt The opttcally

(J,,

acttve (a, 25 = - 19 lo m MeOH) compound

b The stgnal are part of an AA’BB’ system smdll to be measured

IS too

3 showed m the mass spectrum a 1 2 1 trtplet for the

molecular ion at m/z 404,402 and 400, which suggests the presence of two bromine atoms m the molecule on the peak at m/z 400 mdrcated an exact mass of 399 8942, accountmg

resolutton measurement

formula C,,H,, 79Br 0 , which tmpltes 9 degrees of unsaturatton r3C NMR spectrum2(C4DC1,), whtch showed onI> 7 resonances re@on (1 CH and 5 C from DEPT spectrum), thus tllustratmg

lsee Table 1) Of these, 6 were locdted in the sp2

whtle only one methylene

srgnal nppeared tn the htgh field regron

The 5OOMHz ‘H NMR spectrum m CDCl, of 3 showed two D,O exchdngedbie to pherlohc hydroxyl

functron\,

about the 9-10 bond IS slow compared

Chemrcai shtfts and couphng constants 250,JAa=JAa=-135Hz,JAB ofthe lmeshapes

of a 9, IO-drhydrophenanthrene,

tn whtch the rate

with the NMR scale of trme ’

of protons belongtng

= I,a=4Hz

stgnals at 65 58 (2H) dnd 5 49

an aromattc smglet at 6 6 84 (2H), and an AA’BB’ multlplet

centered at 6 2 56 (4H) The last system IS typlcdl of methyfenes

Thesecoupling

for the molecular

nature of 3 was tndtcated by the

The symmetrtcal

a trtcychc structure with two benzene rings

(2H), attrtbutable of inversion

A high

d,,=15Hz,

to the AA’BB’ system (6,= 6, = 2 62, 6, = 6,=

I,, = 2 5 Hz) were determtned

by computer analysis’

(see Ftgure I), and are m good agreement with values prevtously reported for stmtlar compound? constants were used tocalculate

by agenerahzed

’

Karplus equation lothe totston angle C8a_C%ClO-

ClOa, whtch resulted to be 56” The overall stgnals of the mass spectrum nnd the r3C and ‘H NMR spectra delineated 3 as d hexasubstttuted

9- lo-dthydrophendnthrene,

located on each benzene nng expenments, coupling

between

H,-10/9

C-1/8 Thrs assumptton methylene

Postttontng

of thcsc groups wds accomphched

wtch allowed the measutemrnt

resonance

by extensrvc

of mo,t long-rnnge

‘Hmr3C couphng constants

dnd the methane dd 6 113 5 allowed

to locate the unsubstttuted

was corroborated

by the ‘H NOE enhancement

‘Hmr3C decouphng Detectton

of SC&U

aromattc posttlon at

(4%) of the AA’ (6 2 62) part of the

by rrradratton on the methme proton From this result also followed that the signal at 6 2 50

could be atmbuted to the pseudodxial protons, closer thdn the pseudoequatortal t0 the aromattc proton m the conformatton The large coupling respectively)

therefore polystphenol

vrtth one bromme atom and two hydroxyl groups symmetrtcally

constnnts

estdbll\hed

for 3 (\ee below)

of H- l/8 wnh the cdrhons resonatmg

mdrcated their mm relatronshrp

ones (2 44and 3 28 A, respectrvely)

at 6 139 2 and 127 0 (7 6 and 7 9 Hz

” Snrce the ldtter clgnal was also coupled with methylene

protons,

It must be assigned to the 4b/4a posmon, while the former IS due to C-3/6, which must be Imked to n hydroxyl group

557

”i 2 65

LJ-.. I.

2 60

255

2 50

“I..,~J.-“s~~-.

2 60

2 65

Fqpre 1. Observed (left) and calculnted (right) 500 MHz NMR spectraof

on the basis of ns chemical shift The other hydroxyl-beanng

255

2 50

the methylene protons of polyslphenol3

aromatlc carbon (6 143 2) was located at the 2fl

posmon, rather than at 315, because of Its 3 4 HZ couplmg wuh H l/g, a value appropriate too large for a 4JcH ” Consequently,

the bromine dtom must be Imked nt C-4/5

The presence of bulky sub\utuents of themolecule

It IS mterestmg

IS stall symmetnc that the energy

In posItIon 4 and 5 fully agrees with the observed conformational

to note that such a molecule, even afconformatlonally

around a C, rotanonal hamer

between

for an aromatic ‘JcH, but

axls In addlnon,

the two conformer\

the optlcal dctlvlty exhlblted

I\ high enough

ngldlty

blocked and thereforechnal,

to prevent

from compound

then equmbrauon

3 shows at room

temperature The mtngumg phenanthrene

structural

denvatlves

the conformation

among the 9-10.dlhydro-

usrng the MM2 force fieldI

The nnmmum energy conformation 9, IO-dlhydrophenanthrene”

The

effects of the bulky bromme atom\ m posltlon\ 4 and 5, whose repulsion tends to enlarge the angle bndge, whn.h tends to prevent this This results m shghtly folded rings,,

by the dlfferenLe between the C4-C4&‘4b-CS

and C IOa-C4aC4b-CXa

torsion angles (54” and 39”,

with a dihedral angle of 47” between the ring average planes The torsion angle CXa-C9 Cl&ClOa

1s 60” m the calculated Lonformatlon The absolute conflgurdtlon posmve

which are unprecedented

devlatlon from planarity (RMS devlatlon from the mean plane IS 0 05 A) due to

between the rmgs, and ot the dlmethylemc

respectively),

3

behdvlor has been studied prompted us to exdmme m more det;ill

different from that reported for the unsubstuuted

benzene rings show slgrufuauve

as evidenced

of compound

of 3 by molecular mechanics,

(Figure 2) resulted conslderably the anthagomstu.

features

whose conformanonal

rather close to that of 56’ detemnned

of 3 W‘ISe\tdbll\hed

second Cotton effect (MeOH, ~~~~~~ = -444, Ae,,,

dmhenyl chromophore, et &I4 when consldered

dnd therefore nn R contlgurntlon, thdt

from methylene

from IP, CD spectrum = t145)

coupling constants

It dlspldyed d negdtive first and

Thns suggested

a neganve

hehllty

of the

aLcordIng to the CD exclton couplmg method by Mason

the angle between the dromdt:c planes IS less than 90”

558

Figure

2. Drawmg along the C, rotational axls of the mmlmum energy conformatlon polyslphenol3

rn the force field MM2

ofthe

ACKNOWLEDGEMENT The chermcal work was supported by C N R oProgetto Pmallzzdto Clnrnica ~me II, and hy M U R S T (Itdy) Mass spectral data were provided by “Servl?io dl Spettrometna assistance

of the staff 1s gratefully

REFERENCES 1 2 3 4 5

10 11 12 13 14

dl Mas&d de1 CNR e dell’1Jnlverslta dl Napoh” The

acknowledged

AND NOTES

Hodgkin, J H , Craigle, J S , McInnes, A G Cnn I Chm 1966,44, 74 Pedersen, M Phyrochemlsrr~ 1978, 17, 69 1 Glomlxtza, K -W , Sukopp, I , Wxxienfeld, H Planra Med 1985,35,437 Faulkner, D J , m Bromrne Compounds Price D , Iddon, B , Wakefield, D B J , Eds,, p 124, Elsevler, Amsterdam-New-York (1988) Craigie, J S , Gruemg, D E Science 1967, 157, 1058 Kumta, K , Amlya, T , Yabe, K Nrppan Sulsan Cakknlshr 1973,39,973 Chevolot-Mdgueur, A -M , Cave, A , Potter, P , leste, J , Chlxonl, A , Rlche C Phytochemmy 1976, 15, 767 Kuratd, K , Amlyn, T Cizem Lcrr 1977, 1475 Lundgren, I, OlssOn, K , Theander, 0 Actu Chem Scared 1979, B33, 105 Prdcrsen, M , Saenger, P Fries, L PhytorhPmrsfry J 974, 13,2273 Glomblt7a, K -W , Stoffelen, H , Murawsky, U , Blelaczek, J Egg H P[~anta Med 1974,24,301 Katsm, N , Suzukr, Y , Kltamurd S , Irle, T Tetrahedron 1967,2 I, 11X5 Scheuer, P J 1Chemurry of Maruze Natural ProductS, p 89, Academic Press, New York (1973) Yamamoto, 0, Nakamshl, H Tetrahedron 1973,29,781 The system was simulated on an IBM PS/2 70 with the ald of an unpublached program, NMRSnnul by A Mangom Chemical shifts and couplmg Lonstartq were determmed by visual fitting between experimental and calculated hneshapes Haasnot, C A G , de Leeuw, F A M M , Altona, C 7-etrahedron 1980,36,2783 Breltmaier, E, Woelter, W, Carbon-13 NMR Spectroscopy, p 145, VCH, Wemheim (1990) The Chem3D Plus program, provided by Cnmbridge Sclentlfic Computing Inc , on a Apple Macmtosh IIcX wab used for molecular modelhng Caballeira, I, RIOS,M A , Vdsquez, S An Quun Set A 1986, 82, 462 Mason, S F , Seal, R H Roberts, D R Tetrahedron 1974,30, 1671

(Received m UK 11 October 199 1)