310 
PACIFIC SCIENCE, Vol. XXII, July 1968 : 
system (Fig. 17). Generally, extension of an 
enone by an additional conjugated double bond 
causes a bathochromic shift of 30mjx and an in- 
crease of the extinction coefficients in the UV 
spectra. In our case, the transition from DH- 
MTL to MTL, the increment is 45mji and the 
change in intensity is in the opposite direction, 
that is, it is a decrease (hypochromic effect). 
Doubtless this apparent anomaly depends on the 
fact that the new double bond, which is part of 
the planar (pseudoaromatic) 6-membered ring, 
exists in the high energy s-m-conformation. In 
agreement with this is the striking change in the 
spectrum when we compare substances with 
this cyclic chromophore with those which pos- 
sess a formally identical but open chain chromo- 
phoric system. We are dealing here with a tran- 
sition of a cyclic chromophore (with reference 
to the C 4 -C 5 single bond) which has s-c/s- 
conformation to an open chain chromophore 
with the energetically preferred s-trans-confor- 
mation (Fig. 17). Changes of conformation of 
this kind which we have postulated have the 
described effect on UV absorption. If we sub- 
stitute a hydrogen atom in the methyl group 
of MTL, we arrive at a A7-E>H-yangonin, which 
is a type of kawa pyrone that is readily accessible 
by synthesis but has not been found in nature. 
The UV spectra of these compounds are again 
additive from the partial chromophores of MTL 
and substituted toluenes. 
The last group of structural variants with 
respect to degree of hydrogenation is the one 
in which the lactone ring is connected with the 
benzene ring by an ethylene bridge. The best 
known representative of this group is yangonin 
(IT = OCH3, R 2 = FI) (Fig. 18). Since we 
A max 235 m H A max 280 mp 
( £ = 12.500) ( £ = 6.000 ) 
7.8- di hydro -5.6- dehydro- 
methysticin 
^max 285 mp (£ = 11 200 .) 
dihydromethicinic acid 
A max 272 mp ( £ = 20.250 ) 
are now dealing with a fully conjugated system, 
the spectra are no longer simply predictable from 
partial spectra. The increment (A?0 of the 
bathochromic shift is l64m|i for the styryl 
radical in MTL, and the factor for the enhance- 
ment of the intensity of the band is approxi- 
mately 4.4. The dienolide ring is certainly planar 
and we may formulate it as a pseudoaromatic 
system. With regard to position and intensity 
of the absorption band the pyrones agree with 
open chain triene acids as long as one takes into 
consideration the different conformations; how- 
ever they differ markedly from the sepectra 
of the analogously substituted stilbenes. Figure 
18 shows further that spectra of triene acids 
and of their methyl esters do not agree with 
respect to position and intensity of the bands. 
Possibly the ester consists of mixtures of s -cts 
and s -trans conformers with respect to the single 
bond between the carbonyl carbon and the 
adjacent carbon. A study of models of these 
compounds, however, lends no support for 
possible steric hindrance. 
CONCLUSIONS 
From the rhizome of Piper methysticum or 
kawa a number of constituents have been 
isolated which are characterized by remarkable 
pharmacodynamic properties. One may ask why 
these substances with such remarkable properties 
have not found any use in modern therapy, for 
example, as an ataractic or an anticonvulsant. 
A precise answer to this question is not par- 
ticularly easy. There are available a large number 
of chemical compounds, particularly among the 
readily available synthetic ones, which inhibit 
the central nervous system. Testing methods for 
such compounds are well worked out and are 
plentiful. The probability of finding thera- 
peutically useful substances, therefore, is rel- 
atively great. This is particularly so since the 
sedative-hypnotic-narcotic property of a sub- 
stance is not structurally specific. In fact, all 
substances with a given physical-chemical prop- 
erty, for instance, a given partition coefficient 
(relatively high lipid solubility), represent po- 
tential sedative-hypnotic agents. This means that 
in the case of hypnotic-narcotics one is not very 
dependent upon models in nature as is the case 
with other groups of drugs. To this must be 
Fig. 17. UV absorption data of the MTL system. 
