28 Journal of Medicinai ('hemistr?, 1979. I'oi. 22, 2Vo. I
%('(I-
3.6 Hz, H - l ) , 4.7 (9, 1 , H-2). 4.24 (m, 3, H-4, H-5a, H-Sb). 2.46 is, 3, tosyl CH3),2.12 ( q , 2, H-:la, H-rib). 1.37, 1.27 (both P. 6. gem-dimethyl). Anal. (C,3H2006S) C, H. S. 3,5-Dideoxy-j-iodo-1,2-0
[email protected] pentofuranose (24). A solution of 23 (2.5 g), P-butanone is0 mL). and NaI (5 g) was boiled under reflux for 24 h. The same workup as previously described afforded a clear oil that crystallized from cold ethyl acetate-n-hexane as needles hut melted at room temperature: [(i]"D -14.1" ( c 2.8, CHCl,,);N M R (CDCI,,)6 5.86 (d, 1, J1.Z = 3.6 Hz, H - l ) , 4.76 (q, 1, H-2), 4.1 (III. 1. H-41, 3.3k3. 3.40 (both s, 2, H - h , H-sb),2.3 im, 2, H-3a. H-3b). 1.56.1.33 (both s, 6, gem-dimethyl). Anal. Calcd for C8H,,J03:C Found: C, 33.35; H, 4.50. Polarimetric Studies. The procedure used for the periodate oxidation and borohydride reduction has been reported previ~usly.'~~ 9-(S-Deox?-,j-D-er~~hro-pent--l-enofuran(~syliadenine ?' (8)was the reference and was oxidized for 18 h. Because of trans hydroxyl groups, nucleoside 6 a a s oxidized for 5 days. The final solution of dialcohol 7 derived from 6 had [ c i ] , ) +59'. whereas the solution derived from 8 had [ c t ] , ) +55'.
Acknowledgment. This work was supported by Grant CA13802 from the National Cancer Institute. National Institutes of Health. References and Notes 13. .I. Suhaciolnik, "Nucleoside Antibiotics". \Viley-Interscience. New York, XY. 1970, pp 115-119. H. Hoeksema. C;. Slomp. and E. E. van Tamelen. 7 ' ~ i r n hrdron Lett.. 1787 (1964). .J, R . LIcC'arthy, dr.. R. Edr. Kc\.. 11.112 (1WiJ. L. hi. Lerner, ('nrhoh>dr.Re,. .Joseph. and J. H. \Villiams. 4. .-In?, Ch(.m. Soc.. 7 7 . 12 (19551. .J. I'rokop and 11. H. Murray, J . f'harm. Yci., 54, ;359 (1965). I,. €3. 'Townsend in .'Synthetic Procedures in Nucleic Acid C'hemistry", \V. W.Zorbach and K. S. Tipson, Eds.. \Viley-Interscience. Neiv York, NI'. 1973, pp :3?10331. K . S. \{-right. G. Xi. Tener. and H. G. Iihorana, J . Am ('hem. Soc., 80, 2004 (1958). L. Kalvoda, M. Prystag, and F. Sorm. Collect. Czech. Chem. ('cinlrnun.. 11. 788 (19.76). I). Szabo and L. Szabo, .J. Chi.nz. Soc.. 294.1 (1965). t.. G. Kayak and K. I,. FVhistler. ./. Org. C ' h ~ m . 31. . :3Yi9 I lfIG9). I). Si. Brown anti G . H. .Jones. J . ( ' h c , n z . Sot.. ('. 249 (1967). F. Keller. J . E. Hunker. and I,. H. Hrowri. ./. Or,ni.. 102, :{I7 tta. R. Ohki. and S . Nozoe. J . O r p . ('hem. 2 8 . 78:{ i lW3I.
1'. .A I,evene a11d ('omI,ton. ./. [rnpo.I I , 12 I 19661: ( ' h p r n . .4bsir.. 68. 1OC5071f(1968). '1'. Kurihara. H. Takeda. X, Iino. and 'r. Chiba. l h k u g a k u s. ;1nd
F.\Y,\ \ ' l l l l ' t , J . . \ l t Y f
A €3. LIauger, b'.J . Rzeszotarski. C / ? P P ? , . 1.5. 108' 11972).
Ergot Alkaloids. Synthesis of Nit rosourea Derivatives of Ergolines as Potential Anticancer Agents
inhihitor>-activity can he achieved \vith the same moleC~illt..
appear t o inhibit prolactin release frorn the pituitary gland by interacting with the prolact i l l - i n h i b i t i n g factor iPIF) receptor.' As an example. a n t.rXcilin~liiitrosourea could possibly target a tumor located in t ke pituitary gland. Such a compound could he poi t l n t ially usefill in t he treatment of Forbes -Albright S~iitlroinr.a condition which is t h e result of a pituitary t i i t n o r i n which excessive amounts of prolactin are prod leading I O persistent lactation. e .\,'-(k.hloroethyli-S-nitrosoureas 2 decompose (ey F,tyiiliiie.;
iiiiteriiir
1
$4
1
of prolactin release.] Previously. we reported an attempt t o prepare potential irreversible prolactin inhibitors by attaching alkylat.ing groiips at the 8 position c ) f the ergoline skeleton.' As ail C x t e i i S i o n 0 1 ~t h i s w o r k . a i l alkylating nitrosourea group has been incorporated into the ergoline
system in an attetnpt t o prepare compounds which are distrihrlteri in i i i c t i a wav t h a t h c i t l i pr~ila(-tiii; t i i d tiiiiior
0 N-0
RN&-
N-.-CKCH:Cl
-+
R N -C 0 . Y
l l i
2
I ) t o yield an isocyanate and a variety of' other reactive The interaction of' one or more o f these
spec,ic,s 0 ' 1 . '
c 1978 American Chemical Society
