15. 8. 1977

Specialia

Results. GC-MS analysis on 1% OV-17 showed only one p e a k which e x h i b i t e d m/e 138(18) as the molecular ion w i t h a base p e a k at m/e 107 and o t h e r large peaks at m/e 77(16), 53(5), 51(5) and 39(5). Comparison of r e t e n t i o n times (isothermal, 150~ and mass spectra of the unk n o w n m a t e r i a l w i t h those of s y n t h e t i c fl-(o, m, and ph y d r o x y p h e n y l ) e t h a n o l p r e p a r e d by lithium a l u m i n u m hydride reduction of the corresponding m e t h y l esters, p - m e t h o x y m e t h y l phenol and 2 - p h e n o x y e t h a n o l indicated t h a t the n a t u r a l m a t e r i a l was fl-(p-hydroxyphenyl)ethanol. The base peaks of all 3 h y d r o x y p h e n y l ethanol isomers and t h e p - m e t h o x y m e t h y l phenol were identical while t h a t of 2 - p h e n o x y e t h a n o l was m/e 94. The m e t h o x y m e t h y l phenol elutes significantly earlier t h a n t h e hydrox y p h e n y l ethanols and the isomers of the l a t t e r can be distinguished from b o t h their i s o t h e r m a l gas c h r o m a t o g r a m s and their mass spectra. B o t h the m and o isomers h a v e significantly higher m/e 77(35) and m/e 108(67,22). W h e n fl-(p-hydroxyphenyl)ethanol was placed on the perch of a galago, t h e animals responded to it in a w a y

(-)-(R)-l-O-Geranylgeranylglycerol

989

which was n e v e r observed w i t h a n y o t h e r odorants (including its isomers). The galago, slowly and deliberately, placed its open m o u t h o v e r the t r e a t e d spot. This response appeared to place either the inside of t h e m o u t h or t h e b a c k of t h e tongue in c o n t a c t w i t h the perch, and t h u s c o n s t i t u t e d a highly distinctive t y p e of biting behavior. Discussion. Scent m a r k i n g is i m p o r t a n t in the social biology of m a n y primates, and the chest gland of G. crassicaudatus is f r e q u e n t l y utilized as a m a r k i n g gland. Field observations of G. senagalensis indicate t h a t galagos f r e q u e n t l y m a r k t h e i r territories 6 and the chest gland secretion m a y possess an i m p o r t a n t p h e r o m o n a l role for these animals. H o w e v e r , we are unable to i n t e r p r e t t h e p a t i c u l a r significance of the oral p r e s e n t a t i o n to sites m a r k e d w i t h fl-(p-hydroxyphenyl)ethanol and the e x a c t f u n c t i o n of this c o m p o u n d remains to be determined. Nevertheless, with the identification of this first a r o m a t i c c o m p o u n d in the exocrine secretion of a p r i m a t e , it m a y be possible now to explore scent m a r k i n g in p r i m a t e s in t e r m s of defined chemical releasers of behavior.

f r o m the b r o w n alga D i l o p h u s fasciola 1

V. Amico, G. Oriente, M. Piattelli, C. Tringali, E. Fattorusso, S. Magno and L. Mayol

Istituto di Chimica Organica dell' Universit~ di Catania, viale Doria, 1-95725 Catania (Italy), and Istituto di Chimica Organica dell' Universitd~ di Napoli, via Mezzocannone, 1-16-8013d Napoli (Italy), 25 January 1977 Summary. A novel ether lipid, ( - ) - ( R ) - l - O - g e r a n y l g e r a n y l g l y c e r o l (1), has been isolated from the b r o w n alga Dilophus faseiola and its s t r u c t u r e p r o v e d b y spectroscopic m e t h o d s and chemical degradation. A m o n g the b r o w n algae, m e m b e r s of t h e f a m i l y Dictyotaceae are a p a r t i c u l a r l y rich source of new n a t u r a l compounds2. D u r i n g the course of our search for n o v e l met a b o l i t e s of M e d i t e r r a n e a n macroalgae, we h a v e now i n v e s t i g a t e d a further species, Dilophus fasciola (Roth) Howe, belonging to the same family. Material and methods. Chloroform e x t r a c t i o n of the freeze-dried alga gave a green oil which was c h r o m a t o graphed on silica gel using increasing concentrations of e t h e r in light p e t r o l e u m as the eluent. R e p e a t e d chrom a t o g r a p h y of the more p o l a r fractions e v e n t u a l l y resulted in the isolation of ( - - ) - ( R ) - l - O - g e r a n y l g e r a n y l g l y cerol (1) (0.15% yield, d r y w e i g h t of alga) as a colourless, viscous liquid, E~JI~ --2.1 ~ (c 1.5 in CHC13). H.

OR

~OR 1 RfH

2R=Ac

Results and discussion. C o m p o u n d 1, Vmax (liquid film) 3300 cm -1 (OH), had molecular f o r m u l a C~H4003 (high resolution mass s p e c t r o m e t r y m/e 364.2972; calculated for C~3H4003 364.2977). The I R - and U V - s p e c t r a of 1 indicated the absence of c a r b o n y l and c o n j u g a t e d system in t h e molecule. On a c e t y l a t i o n w i t h acetic a n h y d r i d e in pyridine, 1 afforded t h e d i a c e t a t e 2 (M + m/e 448), oily, [~]D --8.4 ~ (c 1.5 in CHCIa), v,nax 1750 cm -1, which showed no h y d r o x y l I R absorption. T h u s 2 of the o x y g e n functions of I were assigned to 2 h y d r o x y l s (which m u s t be vicinal, since 1 gives a p o s i t i v e p e r i o d a t e test), the r e m a i n i n g o x y g e n b e i a g p r o b a b l y i n v o l v e d in an ether link (~max 1150 cm-1). These results and the mass spect r u m which i n d i c a t e d cleavage of t h e molecular ion w i t h

loss of 92 ainu (CzHsO3) suggested t h a t 1 m u s t be a C,0 1-ether of glycerol. Indeed, the P M R s p e c t r u m of 2 in CC14 contains all the required p r o t o n signals3: a) singlets for 2 a c e t y l protons at 6 1.98 and 2.01, b) an A B X s y s t e m (AB-part, 4.20 d, JAB 14 H z ; X - p a r t , 4.98 d, obscured b y o v e r l a p p i n g w i t h the signal of v i n y l protons) which could be assigned to the - C H ( O A c ) C H 2 O A c group and c) a d o u b l e t at 6 3.43 assigned to - C H ~ O - . I r r a d i a t i o n a t 6 4.98 simplified the A B - p a r t into an A B s y s t e m and a t t h e same t i m e collapsed the doublet at 6 3.43 to a singlet. The s t r u c t u r e of t h e additional C,0-moiety could be deduced f r o m t h e r e m a i n i n g P M R signals ~b 1.60 (9H, s, 3 v i n y l Me's), 1.67 (6H, s, 2 v i n y l Me's), 2.03 (12H, m, 6 > C = C H C H 2 - ) , 3.94 (2H, d, J 7 Hz, > C = C H C H ~ O - ) , 5.10 (3H, b, > C = C H C H ~ - ) and 5.29 (1H, bt, > C=CHCH20-)], which closely paralleled those reported 4 for all-trans-geranylgeraniol. A t this j u n c t u r e it b e c a m e a p p a r e n t t h a t t h e new comp o u n d m u s t be represented b y the formula 1, which is also s u p p o r t e d by t h e f r a g m e n t a t i o n p a t t e r n in t h e M S 1 This work was supported by CNR, Rome, Italy. 2 R.E. Moore, J. A. Pettus, Jr, and J. Mistysyn, J. org. Chem. 39, 2201 (1974) ; A. G. Gonzalez, J. Darias, J. D. Martin and M. Norte, Tetrahedron Lett. 7974, 3951; D. R. Hirschfeld, W. Fenieal, G. H. Y. Lin, R. M. Wing, P. Radlick and J. J. Sims, J. Am. Chem. Soe. 95, 4049 (1973); E. Fattorusso, S. Magno, L. Mayol, C. Santaeroce, D. Sica, V. Amico, G. Oriente, M. Piattelli and C. Tringali, J. C. S. Chem. Commun. 7976, 575. 3 In the spectrum of I the 2 OH are seen as a D20-exchangeable , broad singlet at 6 2.65, while the 5 not-exchangeable protons of the glycerol moiety give rise to a complex pattern of signals between 6 3.42 and 3.95. 4 B.A. Nagasampagi, L. Yankov and S. Dev, Tetrahedron Lett. 1967, 189.

990

Specialia

g a v e a p r e p o n d e r a n c e of ( - - ) - ( S ) - m e t h y l - p - t o l y l sulfoxide. Until now higher glycerol ethers with polyisoprenoidic h y d r o c a r b o n c h a i n s h a v e b e e n f o u n d o n l y in e x t r e m e l y h a l o p h i l i c s a n d a c i d o p h i l i c b a c t e r i a % I t is i n t e r e s t i n g to n o t e t h a t all t h e s e lipids, as well as 1, possess t h e ' u n n a t u r a l ' c o n f i g u r a t i o n of t h e glycerol m o i e t y .

w h i c h , besides M + (m/e 364), i n c l u d e s d i a g n o s t i c a l l y imp o r t a n t p e a k s ~ for M+-CsHo (m/e 295), M+-C3HsO a (m/e 272), M+-CsHsO3-CH3 (m/e 257), M+-CaHsO3-C3H 7 (m/e 229), M+-C3HsO3-CsH 9 (m/e 203), M+-C~HsO3-C10H17 (m/e 135), C7H9+ (m/e 93), C6H9+ (m/e 81), C5H9 + (base, m / e 69) a n d Calls+ (m/e 41). The structure was confirmed by reduction with sodium in N H 3 a n d E t O H a t - - 4 5 ~ w h i c h a f f o r d e d a l l - t r a n s 2, 6, 10, 1 4 - t e t r a m e t h y l h e x a d e c a - 2 , 6, 10, 1 4 - t e t r a e n e (M+ m / e 274) as t h e m a i n p r o d u c t , i d e n t i f i e d b y c h r o m a t o g r a p h i c a n d spectroscopic c o m p a r i s o n w i t h a n a u t h e n t i c specimen. Since r e l a t e d , n a t u r a l l y occurring, h i g h e r glycerol 1-ethers (chimyl, b a t y l a n d s e l a c h y l alcohols), all possessing t h e S c o n f i g u r a t i o n , in d i l u t e c h l o r o f o r m s o l u t i o n are s l i g h t l y d e x t r o - r o t a t o r y e, t h e o p t i c a l r o t a t i o n of 1 s u g g e s t e d t h a t t h i s c o m p o u n d could p o s s i b l y possess t h e o p p o s i t e R c o n f i g u r a t i o n . T h i s f e a t u r e was c o n f i r m e d b y u s i n g t h e general m e t h o d for t h e c o n f i g u r a t i o n a l correlat i o n of alcohols d e s c r i b e d b y Mislow v. R e a c t i o n of 1 w i t h p - t o l u e n e s u l f i n y l chloride yielded a m i x t u r e of d i a s t e r e o m e r s w h i c h b y r e a c t i o n w i t h m e t h y l m a g n e s i u m iodide

Synthesis

EXP]~RIENTIA 33/8

5

R. Ryhage and t5. yon Sidow, Acta chem. scand. 17, 2025 (1963) ; E. yon Sidow, Acta chem. scand. 17, 2504 (1963). Y. Toyalna and T. Ishikawa, J. Chem. Soe. Japan 59, 1367 (1938) ; E. Baer and H. O. L. Fischer, J. biol. Chem. 740, 397 (1941); V. Prelog, L. Ruzicka and P. Stein, Helv. ehim. Acta 26, 2222 (1943); V. Prelog, L. Ruzicka and F. Steinmann, Helv. chim. Acta 27, 674 (1944); E. Baer, L. J. Rubin and H. O. L. Fischer, J. biol. Chem. 155, 447 (1944). M.M. Green, M. Axelrod and K. Mislow, J. Am. Chem. Soc. 88, 861 (1966); C. Fuganti and D. Ghiringhelli, Gazz. chim. ital. 99, 316 (1969). M. Kates, in: Ether Lipids. Chemistry and Biology, p. 351. Ed. F. Snyder. Academic Press 1972. M. de Rosa, L. Minale and J. D. Bu' Lock, J. C. S. Chem. Commun. 1974, 543.

6

7 8 9

of (Glu-OMe)Z-litorin

M. Mazzoli a n d R. de Castiglione

Laboratori Ricerche Farmitalia, 1-20146 Milano (Italy), 4 February 7977 Summary. T h e s y n t h e s i s of t h e n o n a p e p t i d e < G l u - G l u ( O M e ) - T r p - A l a - V a l - G l y - H i s - P h e - M e t - N H v c o r r e s p o n d i n g t o t h e f o r m u l a of t h e (Glu-OMe) 2-1itorin, is described. T h e c o m p o u n d h a s t h e s a m e c h e m i c a l a n d biological p r o p e r t i e s of t h e second b o m b e s i n - l i k e p e p t i d e e x t r a c t e d f r o m t h e skin of t h e A u s t r a l i a n frog L i t o r i a a u r e a . W e b r i e f l y r e p o r t t h e s y n t h e s i s of a n o n a p e p t i d e of f o r m u l a < Glu-Glu ( O M e ) - T r p - A l a - V a l - G l y - H i s - P h e - M e t N H z 1 (XI), c o r r e s p o n d i n g t o t h e p r o p o s e d s e q u e n c e of t h e s e c o n d b o m b e s i n - l i k e p e p t i d e of t h e skin of t h e A u s t r a l i a n frog L i t o r i a aurea, i.e. G l u ( O M e ) M i t o r i n ~ . R e l e v a n t inf o r m a t i o n on t h e s y n t h e s i s , a c c o m p l i s h e d b y c o n v e n t i o n a l

< Gtu

Gtu

Trp

As

s o l u t i o n m e t h o d s , is s u m m a r i z e d ill t h e figure a n d t h e table. T h e c o n d e n s a t i o n of Boc-His(Tos) w i t h P h e - M e t - N H 2 v i a t h e Geiger p r o c e d u r e 3 (DCCI + H O B T ) g a v e t h e d e t o s y l a t e d ~ t r i p e p t i d e I (El. ~ = 0.32 His; Es. s = 0.45 His)~. T h e final c o u p l i n g was c a r r i e d o u t b y t h e m o d i f i e d azide Vat

Gty

~i s

Phe

t,4.et

(10) NHNHBoc

II1

NHNHBoc

IV V

NHNHBoc

VI VII

BOC=

Vlll IX

(9) NHNHBoc

Boc

NHNHBoc

Bo,

X NHNH2

XI

Synthesis of Glu(OMe}~-litorin.

I

(-)-(R)-1-O-Geranylgeranylglycerol from the brown alga Dilophus fasciola.

15. 8. 1977 Specialia Results. GC-MS analysis on 1% OV-17 showed only one p e a k which e x h i b i t e d m/e 138(18) as the molecular ion w i t h a...
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