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EuglenapterinЧAn Unusual New Natural Pteridine Derivative from Euglena gracilis.

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rate of formation of the lactone derivative with a natural
configuration on C-15, so it appeared possible to exploit this
effect for the separation of the epimers. For completion of
the other chains the mixture of the aldehydes (12a) and (12b)
is first prepared by reduction of ( l l a ) and ( l l b ) with LiAlH4
followed by reoxidation; subsequent Wittig olefination affords the unsaturated esters (13).
We removed the silyl ether groups in (13) with fluoride
ions to give a mixture of the alcohols (14), without separation
of the epimers. The hydroxy acids obtained on hydrolysis
could be cyclized with a-chloro-N-methylpyridinium iodide
according to the method of Mukaiyama['I to give a mixture
of the lactones (15), which is converted by cleavage of thioketal into the ketones (16) (see Table 1).
Table I . Some physical data of the compounds (6a). (6b], (ISa)+(lSb), and
(160) + (1661; M" determined mass spectrometrically.
( 6 ~ )IR
. (CHCI,): 3040,1600,1740,1720cm-'; 'H-NMR (CDCI,): 6=5.4 ( 2 )m.
4.32 ( 2 )q ( J = 7 Hz), 3.53 ( 2 ) t ( J = 6 Hz). 2.33-3.8 ( 6 ) m. 1.5-2.3 (lo) m, 1.35
( 3 ) 1 ( J = 7 Hz): MS (80°C): m/e=376 (15%. Me),329 ( 5 ) . 303 (43). 191 (58). 145
(100); M v ("CI and '"21): calc. 376.0934, obs. 376.0935 and calc. 378.0904, obs.
378.09 10
(6b), IR (CCI,): 1750, 1730. 1070 cm I ; 'H-NMR (CDCI): 6=5.35 ( 2 ) m, 4.21
( 2 ) q ( J = 7 Hz). 3.97 ( 4 )s, 2.35-3.6 (8) m. 1.44-2.3 (10) m, 1.23 ( 3 )t (5=7 Hz),
1.2 ( 3 ) s: MS (200 'C): m/e=428 (5%. M"), 413 (5). 355 (19.5). 191 (73.5). 163
(23). 145 (100). 87 (96.5)
(ISa)+ (ISb): 1R (CCI,): 1712, 1630 cm '; 'H-NMR (CCI,): 6=6.96, 6.54 ( I ) d
( J = 15 5 Hz). 5.99, 5.96 ( I ) d ( J = 15.5 Hz), 5.2 (2) m, 4.9 ( 1 ) m (H-l5), 4.6 ( 2 ) s
(OCH20). 4.08 ( I ) m ( H - 7 ) . 3.5 ( 4 ) m (OC2H40), 3.3 ( 3 ) s (OCH,), 2.5-3.2 ( 4 )
m. 1.2---25 (12) m. 1.26, 1.22 ( 3 ) d ( J = 6 Hz. C-CHI); MS (160°C): m/e=455
(4'fi. M"). 427 (2). 412 (I). 380 (7). 367 (14). 350 (11). 89 (100); MB calc.
456.2004. obs. 456 2004
(16a) + 1/66): 1R (CCI,): 1728, 1702. 1630 cm I; 'H-NMR (CCI.,): 6=7.69, 7.32
( I ) d (J=16 Hz), 6.31. 6.30 ( I ) d, 5.5 ( 2 ) m, 5.2. 4.6 (I)m (H-15). 4.6 ( 2 ) s
(OCHIO). 4.1 (I)rn ( H - 7 ) . 3.5 ( 4 )rn (OC2H,0). 3.29 ( 3 )s (OCH,), 1.2-2.3 (12).
1.3. 1.21 ( 3 ) d ( J = 6 Hz. C-CHd; MS (380°C): m/e=366 (2%. M a ) , 290 (7.5).
261 (10). 89 (100); MI" calc. 366.2042. ohs. 366.2040
Also in our lactonization technique, no differences attributable to alternative configurations at C-15 could be observed; however, we could confirm the high stereospecificity
of the reduction of the 0x0 group on C-4 in (16) described by
Bartlett14c1.
On reduction with NaBH, ( - 78 "C), the mixture of the C15 epimeric ketones (16) furnished only two easily separable
alcohols, namely (17a) and (17b), of which (1 7a) could be resolved with TiC1, into sterically pure brefeldin A (3), whose
IR, NMR and mass spectra as well as TLC behavior were
identical with those of an authentic sample of the natural
product.
(15a)+(15b): A solution of the seco acid mixture
(14a)+ (14b), H instead of C2H5,in anhydrous acetonitrile
was treated with 250 mg (2.5 mmol) of triethylamine and
then syringed into a refluxing solution of a-chloro-N-methylpyridinium iodide (400 mg, 1.5 mmol) in acetonitrile. The
mixture was allowed to boil for 1 h, the solvent removed in
vacuo, and the residue taken up in ether, washed with 2 N
HCI and saturated NaCl solution, dried over MgSO, and
chromatographed after removal of solvent with ether/petroIeum ether (7 :4);yield 63 mg (68%).
(16a) + (16b): A solution of AgN03 (70 mg, 0.4mrnol) and
N-chlorosuccinimide (70 mg, 0.5 mmol) in acetonitrile (2 ml,
20% HzO) was treated with 6 drops of lutidine and the mixture immediately poured into a solution of the mixture of
(15a) + (15b) (16 mg, 0.035 mmol) in acetonitrile (1 ml). After 1.5 minute's stirring at room temperature a saturated solution of NaHS03 and NaCl was added and the reaction mixture extracted with CH2C12.The organic phase was washed
with 2~ HCI and saturated NaHC03 solution, dried over
MgS0, and, after removal of the solvent in a vacuum, chromatographed on silica gel (ether); yield 11 mg (83%).
Received: January 10. 1980 [Z 473 IE]
German version: Angew. Chem. 92.486 (1980)
CAS Registry numbers:
( I ) , 768-48-9: (31,20350-15-6: (4). 72103-46-9; p a ] . 73816-16-7; (5b). 73816-17-8:
(6a), 73805-63-7; (66). 73805-64-8; (7a). 73805-65-9; (7b). 73805-66-0; (Ha).
73836-96-1; (ab), 73836-97-2; (90). 73805-67-1; (96). 73805-68-2; ( 9 ~ )73805-69.
3; (lo], 73805-70-6: ( I l a ] , 73805-71-7, ( l l b ) , 73836-98-3; fl2a). 73805-72-8:
(l2b). 73836-99-4;(13a). 73805-73-9 (136). 73837-00-0 (140). 73805-74-0 (146).
73837-01-1; (i5a). 73805-75-1; (ISb). 73837-02-2: (16a). 73805-76-2 (16b).
73837-03-3; /i7a], 73805-77-3; (176). 73837-04-4
[ I ] a) V. Osterthun, E. Winrerfeldt, Chem. Ber. 110. 146 (1977);h) Y. Koksal. V.
Osterthun, E. Winrerfeldl. Justus Liehigs Ann. Chem. 1979. 1300.
[2] E. Hiirri. W. Loeffler. H. P. Sigg. H. Stuhelin. Ch. Tamm. Helv. Chim. Acta
46, 1235 (1963).
131 H.P. Sigg. Helv. Chim. Acta 47, 1401 (1964).
[4] a) E. J. Corey, R. H. Wollenberg, Tetrahedron Lett. 1976. 4701; b) E J . Corey. R. H. Wollenberg. D. R. Williams, ibid. 1977, 2243: R Baudon-v, P. Crabbe, A. E. Greene. C. LeDrian. A. E Orr. ibid. 1977, 2973, D. P. Curran, D.
Scholz, Monatsh. Chem. 108, 1401 (1977); c) P. A. Bartletr, F. R. Green. J .
Am. Chem. SOC.100.4858 (1978);d) T. Kitahara, K. Mori, M. Matmi, Tetrahedron Lett. 1979. 3021
IS] M. Grift, R. W. Rickards, Tetrahedron Lett. 1979, 1539.
161 Selectride = Li[(sec-C,H,),BH].
171 A. K. Base, B. La/. W. A. Hoffman, M. S. Manhas, Tetrahedron Lett l97.%.
1619.
[8] E. J. Carey, J:L. G a s , P. L. Ulrich, Tetrahedron Lett. 1975. 617; Mem= methoxy-ethoxymethyl(CH,0C2HIOCH2-).
191 T. Mukaiyama, M. Usui, K. Saigo, Chem. Lett. 1976. 49.
Experimental
(6a): A solution of 5-chloro-1-iodo-I-pentane
(6.5 g, 28
mmol) in anhydrous ether (80 ml) was added at - 78 "C to a
solution of 1 . 6 butyllithium
~
(17.5 ml, 28 mmol) in hexane
and the mixture stirred for 1 h at - 78 "C. A mixture of copper([) 1-pentyn-1-ide (3.67 g, 28 mmol) and tris(dimethy1amino)phosphane (9.2 g, 56 mmol) in anhydrous ether (50 ml)
was prepared in a separate flask and stirred for 0.5 h at room
temperature (yellow-brown solution). This mixture was then
poured slowly at - 78 "C into the solution of the organolithium reagent and the resulting mixture stirred for a further
0.5 h and then treated with a solution of (4) (7 mmol) in anhydrous ether (40 ml). After 1 h the reaction mixture was
poured into 0.5 N HCl, extracted with ether, washed with 2~
HCI and saturated NaHC03 solution, dried over MgS04
and, after removal of the ether, chromatographed on silica
gel (ether/petroleum ether 7:4); yield 2 g (76%).
(6b) was prepared analogously; yield 1.55 g (75%).
Angew. Chem. In/. Ed. Engl. 19 (1980) No. 6
Euglenapterin- An Unusual New Natural Pteridine
Derivative from Euglena grucilis
By Manfred Bohme, Wolfgang PJeiderer, Erich F. Elstner,
and Wilhelm J. Richter"'
The phytoflagellate Euglena gracilis shows both animal
and plant metabolic characteristics. During studies on the
constituents"] of this organism, three components showing
[*I
Prof. Dr. W. Pfleiderer. DipLChem. M. Bohme
Fakultat fur Chemie der Universitat
Postfach 77 33, D-7750 Konstanz (Germany)
Prof. Dr E. F. Elstner
Institut fur Botanik und Mikrohiologie der Technischen Universitat
Munchen (Germany)
Dr. W. J. Richter
Zentrale Funktion Forschung, Ciha-Geigy AG
Basel (Switzerland)
@ Verlag Chemie, GmbH. 6940 Weinherm, 1'280
0570-0833/H0/0606-473 S 02.50/0
473
yellowish fluorescence were obtained after treatment of the
natural material with M n 0 2 in acetic acid solution; they were
regarded as possible unconjugated pteridines. However,
since none of these products could be identified by chromatographic or spectroscopic methods as one of the natural
pterins we have re-investigated them. First of all, the component showing the greatest migration on chromatography on
cellulose with n-propanol/l% ammonia (2/1) (R,=0.48) was
enriched chromatographically and then purified by HPLC
on RP-8 carrier material.
The field desorption mass spectrum (FD-MS) of the isolated material gave a M o o / M H o double signal (m/e=281/
282) corresponding to the molecular formula C I H I5N504,
which was confirmed by the high resolution electron impact
mass spectrum (EI-MS) of the tetrakis(trimethylsily1) derivative obtained by reaction with bis(trimethylsily1)acetamide in
The
pyridine a t 6 0 ° C ( M o o at m/e=569, C23H47N504Si4).
possible structure of a 2-dimethylamino-6-trihydroxypropyl4-0~0-3,4-dihydropteridine
could be deduced from the presence of four silylatable (acidic) H atoms, the characteristic
mass spectrometric fragments, and UV spectra of the various
forms of the molecule, which show a slight bathochromic
shift relative to the pterins. This structure could be confirmed, and the stereochemistry of the trihydroxypropyl side
chain established, by chemical synthesis of all four stereoisomers from 5,6-diamino-2-dimethylamino-4-oxo-3,4-dihydroxypyrimidine (1) and the phenylhydrazones of D- and Larabinose and D- and L-xylose (2) by conventional methods
of pterin chemistryl2I.
0
matographically and spectrometrically identical with the natural products.
Euglenapterin is thus the first example of a novel natural
type of pterin. It remains to be seen whether the structural
modification of the 2-amino group of the pterin system['] is
of general biological and physiological relevance.
Received: January 14, 1980 [Z 474 IE]
German version: Angew. Chem. 92.474 (1980)
CAS Registry numbers:
(I), 61693-31-0; ~-threo-(3),73789-39-6 u-threo-(3). 73789-40-9: ~-erythro-(3),
73789-41-0; D-erythro-(3), 73804214. ~-threo-(3), 4-TMS. 73789-42-1: (4),
73789-43-2; (4). 5-TMS. 73789-44-3; (5)>73789-454: (5). 3-TMS, 73789-46-5; Dxylose phenylhydrazone, 14685-87-1; L-xylose phenylhydrazone, 28640-06-4; Darabinose phenylhydrazone, 28767-74-0; L-arabinose phenylhydrazone, 622- 128
[ l ] E. F. Elslner, A. Heupel, Arch. Biochem. Biophys. 173. 614 (1976).
[2] M. Visconlmi, R. Provenrule, S. Ohlgurt. J. Malleuiulle, Helv. Chim. Acta 53,
1202 (1970).
[3] G. W. Kidder, V. C. Dewey, J. Biol. Chem. 243, 826 (1968).
[4] M. Yoshikuwu. T. Kuto. T. Tukenishi. Bull. Chem. SOC. Jpn. 42, 3505
( 1969).
[SJ W. Pfeiderer, Angew. Chem. 75. 993 (1963); Angew. Chem. Int. Ed. Engl. 3.
114 (1964).
Ozonolysis of 1,2-Dichloroacenaphthylene
By Helmut Seltzer, Siegmar Gab, and Friedhelm Korte"'
Dedicated to Professor Row Huisgen on the occasion of
his 60th birthday
In the ozonolysis of olefins, monomeric normal ozonides
(1,2,4-trioxolanes) are %btained if the cycloaddition of the
carbonyl oxide ( C---O-Oo) to the carbonyl compound
can successfully compete with other stabilizing reactions.
The activity of the carbonyl function and the lifetime of the
carbonyl oxide play a decisive role[']. If both groups are in
one molecule, then intramolecular cycloaddition is preferred,
particularly if the two groups cannot be removed far from
each other spatially after the cycloreversion of the primary
ozonide (1,2,3-trioxolane). In agreement with this, the chlorine-containing ozonides (l),(2), and (3) are formed in high
yields from the corresponding chloroolefins121, while the
affords only small
ozonization of trans-2,3-dichloro-2-butene
amounts of products ascribable to a 3,5-dichloro-1,2,4-trioxoiane131.
>
0
H?
B
c1
Comparison of the C D spectra of the four synthetic products with that of the natural material reveals the side chain to
have the L-threo configuration (3), and that a structural analogy exists with ciliapterin which was isolated from Tetrahymen pyriformi~'~1.
Once the constitution of euglenapterin (3) had been established, the structures of the other two yellow-fluorescing constituents, which had already been recognized as phosphates"], could be assigned as the 3'-phosphate (4) (FD-MS:
M H @at m/e=362; EI-MS after trimethylsilylation: Me'"
of
the expected pentakis(trimethylsily1) derivative at m/e = 721
and characteristic fragmentation) and as the 2',3'-cyclophosphate (5) (FD-MS: M H @ at m/e=344, m a e at m/e=366;
EI-MS after trimethylsilylation: Meo of the tris(trimethy1silyl) derivative at m/e= 559). Phosphorylation of (3) with
POcl, in trimethyl phosphate by the Yoshikawa methodf4',
which preferentially attacks the primary OH function, leads
to good yields of (4) or (5), depending upon the conditions of
work-up. Both substances (isolated as barium salts) are chro-
414
0 Verlug Chemie, GmbH, 6940 Weinheim, 1980
c&:l 0-0 c1
c1
-0
c1
cl@Il
c1
0
The formation of a monomeric ozonide should also be favored on steric grounds in the case of 1,2-dichloroacenaphthylene (4).When (4) is ozonized at 0 ° C in inert solvents,
two stable 0,-addition compounds can be isolated from the
reaction mixture by chromatography on silica gel. On the basis of analytical data the structures (5) and (6) are proposed
for the colorless crystalline
['I
Prof. Dr. F. Korte, Dr. H. Seltzer, Dr. S . Gab
Institut fur Okologische Chemie der
Gesellschaft fiur Strahlen- und Umweltforschung mbH Munchen
D-8050 Freising-Attaching (Germany)
and Lehrstuhl fur Okologische Chemie, Institut fiur Chemie
der Technischen Universitat Munchen
D-8050 Freising-Weihenstephan (Germany)
OS70-0833/(10/0606-474 S 02.50/0
Angew. Chem. Inl. Ed. Eng!. 19 (1980) No. 6
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