Cyclopentenylcytosine (CPE-C, 2), a pyrimidine analogue of the fermentation derived carbocyclic nucleoside neplanocin A, has been synthesized from the optically active cyclopentenylamine 3b by two synthetic routes. CPE-C demonstrates significant antitumor activity against both the sensitive and ara-C resistant lines of L1210 leukemia in vivo. Multiple long term survivors are produced in both tumor models. The compound also gives 100% growth inhibition of the solid human A549 lung and MX-1 mammary tumor xenografts grown in athymic mice. Good activity is also observed against a third human tumor xenograft model, metastatic LOX melanoma. CPE-C has significant activity against both DNA and RNA viruses in vitro. Potent activity is observed against HSV-1 (TK+ and TK-), HSV-2, vaccinia, cytomegalovirus, and varicella-zoster virus. Good activity is also found against a strain of influenza virus (Hong Kong flu), vesicular stomatitis virus, Japanese encephalitis virus, and Punta Toro virus.

A series of 27 hydantoins was prepared and tested as antitumor agents. These were variously substituted in the 5 position but with special emphasis on the substituents (chloro, acetyl, chloroacetyl, and methyl) in the 1 and/or 3 positions. The most active compound was 5,5-bis(4-chlorophenyl)-1,3-dichlorohydantoin with a T/C value of 190% against P-388 lymphocytic leukemia in mice.

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The proofs of the structures proposed for the Chlorobi~rnl pheophorbides 650, fractions 1-3, and for the Chlorobizrn~ pheophorbides 660, fractions 5 and 6, are completed and the degradational evidence, where parallel, confinned through the synthesis of derived porphyrins.The photosynthetic bacteria Clllorobizim thioszilfatoplzilum, strain L and strain VN, contain Chlorobium chlorophyll 650 and Chlorobiz~nz cl~loropl~yll 660 respectivelj., the numbers indicating the wavelength of their absorption maxima in the red. These are magnesium complexes of farnesyl (not phytyl) esters of the Chlorobium pheophorbides 650 and 660. Like ordinary chlorophyll, both these cl~lorophylls are mixtures, for their pheophorbides can be resolved into several con~ponents, which are termed fractions: Cl~lorobium pheophorbide 650, fractions 1-6, and Chlorobium pheophorbide 660, fractions 1-6.These fractions (pheophorbides) are more closely related to the pyrropheophorbide a than to the pheophorbide a from cl~lorophyll a , for they lack the 10-carbomethoxy group of the latter. All were shown to be homologues of 2-(a-hydroxyethy1)-2-desvinyl-pyrropheophorbide a (I, R1 = E t , R2 = Me, R3 = H) (Reaction Scheme 1) and were forinulated (2,3) as shown in Table I , wherein the structures of the related porphyrins as well as soine chlorophyll a derivatives are also indicated. I t will be noted that some trivial names such a s pyrroporphyrin (strictly pyrroporphyrin l5), phylloporphyrin, and desoxo-phylloerythrin are used in two senses. Without qualification, they refer to the prototypes derived from chloropl~yll a ; otherwise, they refer to the homologues of these, derived fro111 the Cizlorobium chlorophylls.The analytical and degradational evidence (2, 3) did not coillpletely prove these structures for, in the absence of special features, it could only reveal the pairs of substituents on positions 1-8 but not their order. In both the 650 and 660 series other structures in which the substituents on any of the pyrrole rings 1, 2, or 4 n-ere reversed in order (e.g. 7-methj~l-8-propionic acid) were equally compatible with it. The indicated structures 1 1 ere preferred, because they \\-ere Inore obviously related to pheophorbide a .In the G50 series, there was no direct evidence concerning the nature of R2 in fractions 3 , 5 , and 6, for citraconimide had not been detected among their oxidation products.In the 660 series, improved analytical methods revealed the natures of R2 in all fractions.However, in the absence of adequate models, the nuclear magnetic resonance evidence xvhich placed the R3 groups on the 6-positions xvas not conclusive (3, 4)

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