Convenient methods for the synthesis of 1-substituted 3-adamantyl chlorides and bromides (2), 1-adamantylphenols and -cresols (3), and 1-adamantylacetic (6) as well as 1,3-adamantanediacetic (11) acids are described. Several novel derivatives were synthesized from these key intermediates: adamantylcyclohexanols (4) and -cyclohexanones (5) from adamantylphenols (3), and esters (7,12, and 22), amides (13 and 18), thioamides (9 and 16), amidine (10), nitrile (15), and amines (14 and 17) from 1-adamantanecarboxylic (19) and -acetic (6) acids and 1,3-adamantanediacetic acid (11). Some adamantylpyrimidines (24) and -purines (25 and 26) were also prepared. Antiviral activities of the compounds obtained in this work and a series of new 1-adamantyl alkyl ketones synthesized before, together with those of some known adamantane derivatives, were tested in vitro on monolayer culture of chick ambryo fibroblasts against Newcastle disease virus.

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New derivatives of 4-homoisotwistane (tricyclo[5.3.1.0(3,8)]undecane) (3), the olefin (8), bromide (4), alcohols (7,9,11, and 14), ketone (10), acid (12), esters (13, 18a, and 18b), amides (5, 16, and 19a-d), nitrile (20), and amines and their hydrochlorides (6, 17, and 21), were prepared, and antiviral activities of these compounds were determined in vitro on a monolayer culture of chick embryo fibroblasts against Newcastle disease virus. 4-Homoisotwist-3-ylamine hydrochloride (6) and 4-homoisotwist-3-ylmethylamine hydrochloride (21) were found 30-50 times more potent than amantadine hydrochloride in this assay. Methods of preparing the test compounds included those functionalization reactions of 3 which revealed many interesting features of the reactivity of the recently discovered polycyclic hydrocarbon 3.

Bromination and hydride transfer-carboxyla-mantane rearrangement of tricycloundecane precursors. Our recent discovery of a convenient synthesis of (I)4 enabled us to study its functionalizations.Reaction of (I) with excess of bromine at room temperature for 10 min gave in 85% yield the 3-bromo-derivative (II),? m.p. 5 9 ~5 " ~ an/e (re1 intensity) 230 (0.2%, M+), 228 IT has been foundlsB that 4-homoisotwistane (tricycle-(0-3%, M+), and 149 (loo%), lH n.m.r. 6 (CCI,) 1-0-2-6 [5,3,1,03~*]undecane) (I)3 is the key intermediate in ada-(complex m), 13C n.m.r.1 (CDCl,) 20.2 (t, l ) , 24.7 (t, 2), 26.3 tion of 4-homoisotwistane (tricyclo[5,3,1 ,03~8]undecane) (I) to give the 3-substituted derivatives (11) and (111) as well as ready hydrolysis of the 3-bromide (11) shows the high reactivity of the 3-bridgehead in the hydrocarbon (I). 7 Satisfactory elemental analyses were obtained for all the new compounds, $ P.p.m. downfield from Me,Si as internal standard. Fine structure on off-resonance proton decoupling and relative intensity of the signals are shown in parentheses.

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