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Statine (STA, 8) and its cyclohexyl analog (ACHPA, 9) are obtained by a stereospecific synthesis via tetramic acid chemistry. Amides of STA and ACHPA, useful for the synthesis of antihyperten-sive renin inhibitors, are prepared directly from the intermediate activated lactams 7 by nucleophilic ring opening with amines.

Statine (STA, 8) and its cyclohexyl analog (ACHPA, 9) are obtained by a stereospecific synthesis via tetramic acid chemistry. Amides of STA and ACHPA, useful for the synthesis of antihyperten-sive renin inhibitors, are prepared directly from the intermediate activated lactams 7 by nucleophilic ring opening with amines.

The mass spectral fragmentation of a series of 10 mitosene analogs is described. Major pathways arise through decomposition of the substituents in the 1 and 10 positions and are unaffected by the substituent in the 7 position. The base peak in the spectrum, in most cases, is represented by the basic mitosene ring. The patterns are general for this series of compounds and may have application in elucidating the structure of the DNA alkylation sites involved in reactions with mitosenes or natural mitomycins.

Oxindole is converted to its dianion by treatment with two equivalents each of n-BuLi and TMEDA. Alkylations with a number of common electrophiles define the scope of synthetically useful transformations leading to 3-monosubstituted and 3,3-disubstituted oxindoles.

Alkylation -deprotection de phenacyl-1 histidinates de methyle N-proteges; obtention d'alkyl-3 imidazolyl-5alanines

NO major English writer contemporary with William Congreve has left such scant information about himself. Biographers have feared, as Edmund Gosse tells us in 1888, that "the opportunity for preparing a full and picturesque life of this poet has wholly passed away."' When Gosse revised his life of Congreve in 1924, he found that the intervening thirty-five years had added practically nothing to our knowledge. But adequate attention has not thus far been given to scattered manuscript materials which might throw light on the life of Congreve. As a means of getting a better picture of our wittiest dramatist, I have examined collections in England, Ireland, and America; and I mention below some of the more significant manuscripts hitherto overlooked by Congreve's biographers. These documents do much to remove the comparative haze in which Congreve has remained. It is hoped that scholars will add to the list until it is possible to know Congreve as intimately as we do the other great literary figures of the period. Congreve's parentage.-The chief source for the history of Congreve's ancient Staffordshire family is The Erdswick Book, a manuscript now in the possession of the head of the family, Sir Geoffrey Congreve, Bart., Chartley Hall, Staffordshire. This manuscript was begun by Sampson Erdswick, the historian, who in 1593 made record of the family genealogy from the early years of the fourteenth century. After Erdswick, the Book was continued in the handwriting of each generation, listing births, baptisms, marriages, deaths, and other miscellaneous information. It is particularly important in showing the poet's relation to the individuals of the large Congreve family, a number of whom are mentioned in his letters and his will. Without The Erdswick Book it would be almost impossible to distinguish between the poet and his four contemporary kinsmen who also bore the name William Congreve. One of these four kinsmen signed documents which have been widely collected and prized as those of the celebrated dramatist. Five of the chief American libraries have among their manuscript collections the papers of this kisman confused with the genuine documents of the dramatist. It is difficult to understand how The Erdswick Book could have been so long overlooked. Also important for the history of the poet's family is the file of Congreve papers kept at the William Salt Library, Stafford. These papers

* The leading character in the English version, Squire Trelooby, is represented as a native of Cornwall, and the name is derived, no doubt, from the Cornish mining term treloobing, the act of " stirring and working the loobs, or slimy earth of tin, in a slime-pit, that the mud may partly wash off with the water and the ore settle at the bottom " (Century Dictionary). The name Trelooby might well have been suggested by Congreve as a result of his friendship with Walter Moyle, a native of Cornwall, to whom we find Congreve writing on August 13, I695, Moyle at that time being absent from his London friends to conduct his campaign for a seat in Parliament. In the letter Congreve refers incidentally to the Comish miners. See The Whole Works of Walter Moyle, Esq. (London, 1727), pp. 227-229. t See, for example, C. W. Ward, Sir John Vanbrugh (London, 1893), I, 1-lii. $ Issued from the Nonesuch Press in four volumes, London, 1923. Squire Trelooby is included in the third volume, pp. I I i-i 58. ? The reviewers of Mr. Summers's edition of Congreve have very generally accepted the inclusion of Squire Trelooby without protest. Mr. Allardyce Nicoll, however, in The Year's Work in English Studies for 1923, p. 154, asserts that "there is not a whit of evidence to associate Congreve with the quarto as printed, indeed he himself, in a letter, disowned it; contemporaries were quite well aware that it was not his. Its inclusion in Mr. Summers's edition, therefore, can be allowed only on sufferance, and future biographers of Congreve should call attention to the fact that the printed quarto in all probability has nothing to do with Congreve whatsoever." This statement is not altogether consistent with Mr. Nicoll's praise (The Year's Work in English Studies for 1924, p. 189) of Sir Edmund Gosse's "eminently careful and discriminating" discussion of the Squire Trelooby puzzle, for Sir Edmund Gosse (Life of Congreve (London, I924), p. 137) is not at all certain . . . that this Squire Trelooby of 1704 does not virtually represent "the work of Congreve and his two collaborators.

When Dryden read the manuscript of William Congreve's Old Bachelor in 1692, he pronounced it the best “first play” that he had ever seen. Dryden's appreciation of Congreve's first play has been seconded by later critics. Dr. Jonson, for instance, found the comedy “the work of very powerful and fertile faculties; the dialogue ... quick and sparkling, the incidents such as seize the attention, and the wit so exuberant that it ‘o'er-informs its tenement.‘” Macaulay pronounced it “inferior indeed” to Congreve's “other comedies, but, in its line, inferior to them alone.” The dialogue, continued Macaulay, “resplendent with wit and eloquence ... preserves a certain colloquial air, a certain indescribable ease, of which Wycherley had given no example and which Sheridan in vain attempted to imitate.”

For a man contemporary with Addison, Swift, and Pope, men quite near to us through personal letters and biographies, Congreve remains peculiarly apart and obscure. To get at his personality, more attention should be given to his letters. These, unfortunately, have not been preserved in large numbers; and the disorder in which the extant letters have remained has misled every biographer and brought about misinterpretations. Arranged in proper order, the letters clear up obscure references and give insight into the character of the writer. They deserve more careful study than they have hitherto received from biographers who have attempted to gain, and have despaired of gaining, an intimate knowledge of our wittiest dramatist.

Alkylation -deprotection de phenacyl-1 histidinates de methyle N-proteges; obtention d'alkyl-3 imidazolyl-5alanines

A series of 1-substituted mitosene analogues of the mitomycin antitumor antibiotics was prepared by total synthesis and screened for activity against P388 leukemia in mice. In general, analogues with moderately good leaving groups (mostly esters) at the 1 position were active, whereas analogues without such substituents were inactive or barely active. These results lend support to the idea that mitosenes with leaving groups at position 1 are capable of bifunctional alkylation of DNA in a manner similar to that of mitomycin C. The most active mitosenes were equal in potency (minimum effective dose) to a corresponding aziridinomitosene, but they were less effective in prolonging life span.

Publisher Summary This chapter discusses the different antihypertensive agents and their therapeutic efficiency. The chapter also discusses their potential to have positive or at least neutral effects on other factors, such as serum lipids, glucose tolerance, or potassium excretion. Major developments include clinical reports on the effects of intravenous administration of renin inhibitors and reports of the orally active renin inhibitors in primate models. Molecular modeling has suggested cyclic conformational constraints that are compatible with in vitro renin inhibition. The identification of a putative angiotensin II receptor gene indicates progress toward the development of biochemical tools and molecular models that will facilitate the development of angiotensin II antagonists. Molecular biology techniques are being used to provide a more detailed analysis of the angiotensin converting enzyme (ACE). The importance of tissue ACE over plasma enzyme in the long-term regulation of blood pressure has been described and the presence of ACE in vascular tissue and its inhibition has been demonstrated in rats. A combination ACE inhibitor-p-blocker has been reported to lower diastolic blood pressure with efficacy equivalent to enalapril and similar renovascular effects. The α-1 adrenoceptor and α antagonists for the treatment of hypertension have been discussed in the chapter. Animal models for the detection of post-junctional α-2 selective antagonists have been developed. Flosequinan, a direct-acting vasodilator, is effective in essential hypertension as well as in severe congestive heart failure. Two adenosine receptor agonists, PD 117519 and SC 32796, are relatively selective for adenosine A1 vs. A2 receptors and lower blood pressure without tachycardia in several hypertensive animal models. A contractile peptide substance termed “endothelin” has been isolated from porcine aortic endothelial cells. Research on endothelin is progressing rapidly and opportunities for new antihypertensive drug discovery should become evident in the not too distant future.

DID William Congreve write the ballad of three stanzas that is sung by Ben, the sailor, in the third act of Love for Love, or did he borrow it from a broadside ballad of six stanzas printed more than twenty years before the play? The latter is the only tenable view if we accept the findings of Mr. F. Burlington Fawcett in his recent edition of the Osterley Park Ballads. The sixty-first ballad of this famous collection is the same, in the first three of its six stanzas, as Ben's song in Love for Love. The ballad is entitled "Buxom Joan of Lymas's Love to a Jolly Sailer: or, The Maiden's Choice: Being LOVE for LOVE again. To an excellent new Play-house Tune. London. Printed for P. Brooksby, at the Golden-ball in Pye Corner."' This P. Brooksby, according to Mr. Fawcett, had his shop in "Pye Corner" from 1635 until 1672, and in West Smithfield from 1672 until 1695, the year of his death. If these dates are correct, the ballad was evidently printed as early as 1672, at least twenty-three years before the play; and the editor specifically assigns the ballad to that period. It is not easy, however, to overlook the suggestion in the title that the ballad was taken from the play: "Being LOVE for LOVE again. To an excellent new Play-house Tune." Certainly it was a very common practice for the vendors of broadside ballads to appropriate the popular songs of the plays. "Being sung in the last new play" or "An excellent new playhouse song" are typical of frequent advertisements in ballad titles. Except that the earlier date is, according to Mr. Fawcett, indicated by the place of publication, we should have little hesitancy in deriving the "Buxom Joan" from Love for Love, acted in April, 1695. Can Mr. Fawcett be mistaken in his dates? In an effort to verify them by means of the Term Catalogues, I find P. Brooksby listed repeatedly in West Smithfield between 1673 and 1681; but the next listing after 1681-for 1692reads as follows: "Printed for P. Brooksby at the Golden Ball in Pye Corner."2 Although the only later entry in the Catalogues for P. Brooksby-during the Easter term of 16963-unfortunately does not state the location of the publisher's shop, it was no doubt still "Pye Corner," since ballads printed for him at that place can be dated unquestionably during the years following 1692.4 Thus it is evident that the place of publication can have no weight in dating the ballad before the play. Congreve's latest biographer, Mr. D. Crane Taylor, argues that Congreve has borrowed from the broadside ballad of six stanzas chiefly because of the