Bicyclomycin 1 is an antibiotic that is isolated from a culture filtrate of Streptomyces sapporonensis and Streptomyces aizunensis. Bicyclomycin exhibits a low toxicity and also possesses a unique chemical structure. Model studies of the synthesis are presented, however the total synthesis was not realized. The critical reaction involves oxidative cyclization of a methylidenepiperazinedione to the bicyclo {4.4.2} system under basic conditions. This is then elaborated to include the carbon framework of the side chain. The two amides are protected throughout the model synthesis and possible protecting groups are described for an eventual total synthesis of bicyclomycin.

Part I. Several azoalkane-triplet sensitizer bichromophoric systems are synthesized and the energy transfer properties are studied. Intramolecular energy transfer to azoalkanes is found to be much slower than literature cases with aromatic hydrocarbon acceptors. This is the first study of intramolecular energy transfer to a small chromophore. Energy transfer efficiencies are studied by measurement of phosphoresence intensities and lifetimes in low temperature glasses. Polymethylmethacrylate is used as a rigid matrix for some emission studies. Competitive intra and intermolecular quenching experiments and the corresponding Stern-Volmer plots are used to determine energy transfer rates in solution. Eventually a bichromophoric system (AP-DBO) is synthesized that has both the desired rapid intramolecular energy transfer and a quenchable azo triplet lifetime of (TURN)7 ns. Attempts to observe the azo triplet by transient techniques are unsuccessful. The triplet energies of several azos are estimated by kinetic spectroscopy using a graded series of sensitizers and the singlet-triplet energy gap is found to be constant at about 20 kcal/mol. Part II. The photochemical isomerization of azo-1-bicyclo 2.2.1 heptane is studied on long and short wavelength irradiation. Long wavelength irradiation yields (PHI)(,c(--->)t) = (PHI)(,t(--->)c) = 0.5. Isomerization quantum yields on 193 nm irradiation from an ArF laser are much lower than 0.5 and some deazatization occurs. An energy level diagram is presented to account for the observed results. Attempts are made to determine the triplet energy of cis-axo-1-bicyclo 2.2.1 heptane utilizing kinetic spectroscopy. The large triplet sensitized (PHI)(,c(--->)t) combined with the lability of the compound thwarted this investigation.

Two bicyclic azoalkanes were prepared: 1-cyclopropyl-2,3-diazabicyclo 2.2.2 oct-2-ene (MCP) and 1,4-dicyclopropyl-2,3-diazabicyclo 2.2.2 oct-2-ene (DCP). Products derived from the photolysis of MCP and DCP were the typical bicyclo 2.2.0 hexanes and 1,5-hexadienes; however, the cyclopropylcarbinyl rearrangement was also influential in product formation especially in sensitized irradiations. A mechanism for product formation is presented in which a biradical spin correlation effect is invoked. A mechanism is present for excited state azoalkane decomposition through the ('1)(n,(pi)*) and ('3)(n,(pi)*) states without intersystem crossing (isc) between the two spin states. Maximum quantum yields for isc are calculated as 0.092 and 0.049 for MCP and DCP, respectively. Photophysical data and product ratios support the mechanism. Photolysis of MCP in CCl(,4) is rationalized by an electron transfer process from MCP to CCl(,4). Efforts to discover other electron acceptors which would undergo chemical reactions have failed; however, quenching of the fluorescence lifetime was observed and the data are presented.

The first isolable hydrocarbon derivative of methylenecyclo- propene, 1,4-di-tert-butylmethylenecyclopropene, was synthesized. The chemical shifts of the olefinic protons revealed that the dipolar structure Ia makes a sizeable contribution to the resonance hybrid. (DIAGRAM, TABLE OR GRAPHIC OMITTED...PLEASE SEE DAI) Methylenecyclopropene was generated in vacuo in approximately 10% yield by dehydrochlorination of 2-chloromethylenecyclopropane using potassium tert-butoxide in tetrahydrofuran at -40(DEGREES)C and 0.5 torr. Nearly pure methylenecyclopropene could be prepared from the same precursor using a vertical column containing potassium tert-butoxide supported on Chromosorb W at 240(DEGREES)C and 10 mtorr. The nuclear magnetic resonance spectra (('1)H and ('13)C) were obtained at -100(DEGREES)C in tetrahydrofuran-d(,8). The exocyclic protons appear at (delta) 3.47 and the ring protons at (delta) 8.61. The exocyclic carbon resonates at (delta) 59.57 and the ring carbons at (delta) 132.90. The infrared spectrum was recorded at 15 K in an argon matrix. These chemical shifts and the presence of a strong transition in the infrared at 1770.3 cm('-1) show that IIa is an important contributor to the structure of methylene- cyclopropene. (DIAGRAM, TABLE OR GRAPHIC OMITTED...PLEASE SEE DAI) The vapor phase dehydrochlorination of either 1,4-dichlorospiro- pentane or 1-chloro-2-vinylcyclopropane over supported potassium tert-butoxide at 320(DEGREES)C and 10 mtorr yielded 1-vinylcyclopropene. Other supported reagents studied include methyllithium on glass helices and tetrabutylammonium fluoride on glass helices. These can be used to generate cyclopropenes from vicinal dihalocyclopropanes and (beta)-halosilanes, respectively. For example, 1-chlorocyclopropene, 1-chloro-2-trimethylsilylcyclopropene, 1-bromo-2-chlorocyclo- propene, bicyclo 4.1.0 hept-(1,7)-ene and bicyclo 4.1.0 hept- (1,6)-ene were synthesized by gas phase elimination reactions over these reagents.

The Saframycins are naturally occurring antibiotics with an interesting bisquinone structure. The first and only synthesis of saframycin B is described herein. The interesting aspects of this synthesis are the convergent approach and the method of stereochemical control. Studies directed towards adapting the saframycin B synthesis to the synthesis of saframycins A and S are also described. These studies have resulted in the synthesis of a compound structurally related to the saframycins but so far unreported in the literature. (DIAGRAM, TABLE OR GRAPHIC OMITTED...PLEASE SEE DAI)

1-Bromo-2-chlorocyclopropene (BCC) was prepared by treating 1-bromo-2,2-dichlorocyclopropyltrimethylsilane with tetrabutylam- monium fluoride in tetrahydrofuran at -20(DEGREES)C. Diels-Alder reactions of BCC with 1,3-dienes provide 1,6-dihalobicyclo 4.1.0 hept-3-enes which can be treated with potassium tert-butoxide in tetrahydro- furan to give the corresponding cycloproparenes. This approach was used successfully to prepare benzocyclopropene, 1H-cyclo- prop b anthracene, bis-cyclobutabenzocyclopropene, bis-cyclo- pentabenzocyclopropene, and 1H-2,3,4,5,6,7,8,9-octahydrocyclo- propa 1 phenanthrene. Tetrabutylammonium fluoride supported on glass helices was used to generate strained double bonds from (beta)-halosilanes in the gas phase. Bicyclo 4.1.0 hept-1,7-ene and bicyclo 4.1.0 hept-1,6- ene were prepared and their thermal chemistry investigated. Bicyclo 4.1.0 hept-1,7-ene undergoes Ene type reactions to give two dimeric cyclopropene products. One (25) is stable at room temperature and the other undergoes a second dimerization via a 2+2 cycloaddition to give a tetramer. Bicyclo 4.1.0 hept-1,6-ene also undergoes an Ene type reaction to give 25. Cyclopropene (25) was observed to undergo a thermal epimerization reaction at 25(DEGREES)C by way of a vinyl carbene intermediate. Reaction of 1-trimethylsilyl-2,2-dichlorobicyclo 4.1.0 heptane with the supported fluoride gave only 2-chloro-1,3-cycloheptadiene.

S-Adenosylhomocysteine Hydrolase (SAHase) catalyzes the reversible hydrolysis of S-adenosylhomocysteine (SAH) to adenosine and homocysteine in an addition-elimination mechanism. This mechanism could follow one of four possible stereochemical pathways. To distinguish between possible pathways, 5'(R)-(5'-('2)H(,1))-adenosine, 5'(S)-(5'-('2)H(,1))-adenosine, 5'(R)-(5'('2)H(,1))-SAH, 5'(S)-(5'('2)H(,1))-SAH, (E)-(5'-('2)H(,1))-4',5'-dehydro-5'-deoxyadenosine, and (Z)-(5'-('2)H(,1))-4',5'-dehydro-5'-deoxyadenosine were chemically synthesized. SAHase was isolated from calf liver. Incubation of the stereospecifically deuterated adenosines and homocysteine with SAHase gave SAH with retention of configuration at C-5'. Addition of homocysteine to the (E) and (Z) isomers of (5'-('2)H(,1))-4',5'-dehydro-5'-deoxyadenosine by SAHase occurred with syn geometry. Therefore, the overall reaction is a syn elimination-syn addition process, indicating a single base mechanism. A variety of nucleoside analogs have been shown to inactivate SAHase. Several different mechanisms of inactivation have been suggested. However, none of the inactivators appear to be suicide substrates. Analogous to the reaction of 3-decynoyl-S-NAC with (beta)-hydroxy decanoyl dehydrase, an acetylenic derivative of adenosine would be expected to undergo propargylic rearrangement upon activation by SAHase. The synthesis of acetylenic adenosine is described, as well as the radiolabelled 2-('3)H -acetylenic adenosine and 6'-('3)H -acetylenic adenosine. The irreversible inhibition of acetylenic adenosine on SAHase is dependent on both time and inhibitor concentration. The K(,i) was determined to be 173 nM. Binding studies conducted with radiolabelled acetylenic adenosine showed a binding stoichiometry of 4 moles of acetylenic adenosine per mole tetrameric enzyme. Aristeromycin is one of the better inactivators of SAHase. Binding studies between biosynthetically prepared 2-('3)H -aristeromycin and SAHase were conducted. A binding stoichiometry of 2.5 moles aristeromycin per tetrameric enzyme was determined.

The biosynthesis of the antibiotic aristeromycin (1), produced by Streptomyces citricolor, has been investigated. Incorporation experiments using (('13)C)- and ('3)H, ('14)C -labelled forms of glucose have shown that the carbocyclic portion of aristeromycin is derived from glucose. Further studies revealed some interesting mechanistic details of the ring formation. Precursor incorporation studies have also shown that the adenine moiety from adenosine is incorporated intact into the antibiotic. Administration of (1,2-('13)C(,2))-glycine and (2-('13)C,('15)N)-glycine has shown that C-2 of glycine is incorporated into C-2, C-5, and C-8 and C-1 of glycine into C-4 of the adenine moiety of aristeromycin. The antibiotic and antitumor agent neplanocin A (4) has been successfully isolated from S. citricolor, and results from precursor incorporation experiments suggest that the biosyntheses of aristeromycin and neplanocin A are closely related.

Rates for the two sequential steps of the Arbuzov rearrangement: (UNFORMATTED TABLE FOLLOWS) MeI ABPOMe (--->) ABP(O)Me, A, B, = OMe, OMe;(TABLE ENDS) OMe, Ph; Ph, Ph; OMe, Et; and Et, Et were measured by conductivity. The concentration of the methoxyphosphonium iodide intermediates was determined from calibration curves relating conductivity to concentration for the analogous stable ethylphosphonium iodides. No significant contribution from the autocatalytic Arbuzov rearrangement: (UNFORMATTED TABLE FOLLOWS) ABP('+)(OMe)Me ABPOMe (--->) ABP(O)Me,(TABLE ENDS) was observed for these reactions. For all cases except methyl diethyl- phosphinite (A = B = Et), the rate determining step is the alkylation of the trivalent phosphorus ester. Rates for the autocatalytic Arbuzov rearrangement of the same compounds were measured by ('31)P nmr. The substituent effect ((rho)(,I)) for the reactions was determined by correlation of the kinetic data with the sum of the Taft inductive parameters ((sigma)(,I)) of the substituents on phosphorus. The (rho)(,I) values for the two steps of the "textbook" Arbuzov rearrangement are -4.6 and 5.6 respectively. The (rho)(,I) for the autocatalytic Arbuzov rearrangement is 0.75.

1H-Cyclopropa b phenanthrene (33) was synthesized in 89% yield by dehydrohalogenation of la-bromo-9a-chlorola,2,9,9a-tetrahydro-1H-cyclopropa b phenanthrene 43 with potassium t-butoxide in THF at -20(DEGREES)C. A key step in the synthesis of 33 was the Diels-Alder reaction of 1-bromo-2-chlorocyclopropene 38 with 1,2-dimethylene-1,2,-3,5,6,7,8,9-octahydronaphthalene (41). The compound did not exhibit any unusual spectral properties. 1,2-Dihydrocyclobuta b phenanthrene 49 was also synthesized via the cycloaddition of 41 with dimethyl cyclobutene-1,2-dicarboxylate. Cycloproparenes incorporating a second ring fusion were prepared via the Diels-Alder reaction of 38 with various dienes, followed by dehydrohalogenation of the Diels-Alder adducts with potassium t-butoxide. This method permitted the synthesis of the symmetrically annelated 3,4,5-trihydro-1H-cycloprop f indene 67 and 3,4,5,6-tetrahydro-1H-cyclopropa b naphthalene 69, as well as the asymmetrically annelated compounds 4,5,6-trihydro-1H-cycloprop e indene 71 and 4,5,6,7-tetrahydro-1H-cyclopropa a naphthalene 73. The nonlinearly fused cycloproparenes 71 and 73 were treated with several electrophiles to determine the degree of regioselectivity of cleavage of the three-membered ring. Compound 71, containing the five-membered second ring annelation, was highly regioselective with most electrophiles, giving either the alpha- or beta- substituted indans. Compound 73, containing the six-membered second ring fusion, gave a mixture of alpha- and beta-substituted tetralins with all reagents. The high regioselectivity of 64 has been attributed to rehybridization of the orbitals due to the additional strain imposed by the second ring fusion.