COMMUNICATIONS TO THE EDITOR
6454
VOl. 80
A NEW BIOLOGICALLY ACTIVE NAPHTHOQUINONE’
The yellow oil has antihemorrhagic a c t i ~ i t y . ~ It restored both oxidation and phosphate esteriSir: fication when added to light-treated extracts and Indications of apparent involvement of quinones was 3 times more active than vitamin K1 in oxidaas coenzymes in cellular metabolisni2J prompts us tion and 6 times in phosphorylation. The P/O to report findings concerning a new naphthoquinone ratio observed with the natural compound was in hfycobacterium phlei. With extracts of M . phlei 1.35, whereas it was only 0.68 with a concentration wliich have been irradiated to destroy naphtho- of vitamin K1 which gave maximal restoration. quinones, restoration of oxidative phosphorylation Restoration also occurred with K1-naphthoquinis specifically dependent upon the addition of vita- ones, vitamin K1 being the most active, while Kzmin K1 or a closely related 2,3-dialkyl-1,4-naphtho-homologs containing 2 and 3 isoprene units q~inone.~ The active substance4 has now been showed only slight activity.l0 identified as a naphthoquinone. Quinones isolated from beef heart mitochondria The naphthoquinone was extracted from washed participate in electron transportll whereas a syncells (450 g., wet) by refluxing with 2,2,4-trimethyl- thetic quinone was used to restore oxidation and pentane-2-propanol (3 : 1). Extraction with ace- phosphorylation12 with mammalian mitochondria. tone then gave a product which was chromato- l h e new naphthoquinone is unique in that it is graphed on Decalso. The naphthoquinone (10 found in mycobacterial extracts capable of phosrng.) was eluted as a yellow oil with petroleum phorylation and is more active than any other ether-ether (49 : 1). quinone tested in restoring oxidative phosphorylaThe absorption spectrum is identical in position tion. The monophosphate ester may exist as the 243, 249, 261, 270, active intermediate in oxidative phosphorylaand relative intensities (Ago80xc.tsne 328 and a shoulder a t 240 mp) with those of vita- tion.2.4,13-16 mins K1 and & while the indicated a maxi(9) We wish to express our appreciation to Dr. J. Vitnle, Harvard niuin mol. wt. of 620. Comparison of the infrared School of Public Health, for assaying this compound. (10) A. F. Brodie, Federation Proc., 17, 196 (1958). spectrum with those of the homologs of vitamins (11) Y. Hate& R . L. Lester and T. Ramasarma, i b i d . , 17, 238 I ( 1 and K2 showed identity in the position of the (1958). peaks with the former but marked differences from (12) R . E. Beyer, Biochim. et Biophys. A c t a , 28, 663 (1958). the latter. The intensity of the C-H stretching (13) J S. C. Wessels, Rec. f r a v . c h i n . , 73,529 (1954). (14) K. Harrison, Nature, 181, 1131 (1958). and bending vibrations indicated more than 25 (15) V. M. Clark, G . W. Kirby and A. R . Todd, Natfcre, 181, 1650 saturated carbon atoms in the molecule. The (1958). compound gives positive Dam-Karrer5 and Alm(16) T. Wieland and F. Pattermann, Angew. Chcm , 7 0 , 313 (1958). quist-Klose6 tests, a negative Craven test7 and is LEONARD WOODMEMORIAL LABORATORY destroyed by light a t 360 mp. OF BACTERIOLOGY AND IMMUNOLOGY DEPARTMENT MEDICAL SCHOOL A, F. BRODIE Chromatography on Vaseline-impregnated paper HARVARD MASSACHUSETTS with methanol-2,2,4-trimethylpentane (3: l ) , sol- BOSTON, OF CHEMISTRY B. R. DAVIS DEPARTMEXT vent I , or methanol-2,2,4-trimethylpentane-2- HARVARD L F. FIESER UNIVERSITY propanol (3: 1: l), solvent XI, revealed a difference CAMBRIDGE, MASSACHUSETTS RECEIVED OCTOBER24, 1958 from all known K-homologs.8 I
Compound
Naphthoquinone ex 111. phlei K, series: side chain Cr ClO
.81
C?5
.53 .%7 .I7 .12
C30
..
el6 e 2 0
Vitaniin K2
0.06
.I5
RI
I1
0.10 .S8 .75
.56 .41
.25 .14 .26
Comparison of the UV and IR spectra of the oily hydroquinonediacetate with those of the corresponding derivative of vitamin K1 revealed differences similar t o those between the parent compounds (Azz:tana 233, 278 and 258 mp). (1) This investigation was supported in part by research grants E-827(C4) from the National Institute of Allergy and Infectious Diseases and CY-1696 (C5) from the National Cancer Institute, of the National Institutes of Health; and by the Milton Fund of Harvard University. (2) A . F. Brodie. M. M. Weber and C. T. Gray, Biochim. el Biophys. A c f a . 2 5 , 448 (1957). (3) R. L. Lester, F. L. Crane and Y.Hateti, THISJOURNAL, 80, 4751 (1958). ( 4 ) A . F. Brodie, Abstracts of Papers, 132nd meeting. American Chemic:il Society, New ’I’ork, New York, Sept. 1857, p. 52-C. (5) H . Dam, P. Karrer, et ul., Helu. Chim. Acta, 22, 310 (1939). (fj) 1 3 . 1. Almyuist and A . A. Klose, Tms JOURNAL, 61, l f i l O (1939). (7) R. Craven, J. Chem. SOL.,ltiO5 (1931). (8) We wish to express our appreciation t o Dr. 0. M e r , F. Hoffman 1,aRoche and C o . , for a generous supply of these compounds.
THE PREPARATION OF PHOSPHORUSCONTAINING HETEROCYCLES BY REACTION OF PHOSPHINE WITH ALDEHYDES
Sir: The reaction of phosphine with aliphatic aldehydes has been investigated previously and the products usually obtained were tetrakis-(l-hydroxyalkyl)-phosphonium 4 RCHO
+ PHs + H X R
=
-+ (RCHOH)hP(+’X‘-) H or n-alkyl group
We have found that this reaction takes a different course with alpha-branched aldehydes and leads to the formation of secondary phosphines which are derivatives of a novel heterocyclic system, 1,3-dioxa5-phosphacyclohexane. H
C I l R R,
( 1 ) J. Messinger and C. Engds. Bcr., S i , 326 (1888).
(2) A. Hoffman, THIS JOURNAL, 43, 1684 (1921). (3) A. Hoffman, i b i d . , 62, 2995 (1930). (4) W. A. Reeves, F. F. Flynn and J. D. Guthrie, ibid., 77, 3923 [ 1956).
