Probes for narcotic receptor-mediated phenomena. 33. Construction of a strained trans-5,6-ring system by displacement of a nitro-activated aromatic fluorine. synthesis of the penultimate oxide-bridged phenylmorphans

The synthesis of the ortho- and para-e isomers in the oxide-bridged 5-phenylmorphan series of rigid tetracyclic compounds was accomplished via rac-5-(2-fluoro-5-nitrophenyl)-2-methyl-2-azabicyclo[3.3.1]nonan-9beta-ol ((+/-)-10), an intermediate containing an aromatic nitro-activated fluorine atom. The fluorine atom was used as the leaving group for the formation of the strained tetracyclic trans-fused 5,6-ring system in rac-(1alpha,4aalpha,9aalpha)-1,3,4,9a-tetrahydro-2-methyl-6-nitro-2H-1,4a-propanobenzofuro[2,3-c]pyridine ((+/-)-11), although preference for cis ring fusion during the formation of tricyclic tetra- and hexahydrodibenzofurans has been well-documented. Single-crystal X-ray crystallographic study of the desired para-e isomer ((+/-)-2), as well as of two intermediates in its synthesis, provided assurance of the correct structures. The e-isomers are among the last of the 12 oxide-bridged 5-phenylmorphans to be synthesized. We envisioned the syntheses of these rigid, tetracyclic compounds in order to determine the three-dimensional pattern of a ligand that would enable interaction with opioid receptors as agonists or antagonists.     

Projective Multi-Resolution Analyses for L<Superscript>2</Superscript>(ℝ<Superscript>2</Superscript>)

We define the notion of projective multiresolution analyses, for which, by definition, the initial space corresponds to a finitely generated projective module over the algebra C(Tⁿ) of continuous complex-valued functions on an n-torus. The case of ordinary multi-wavelets is that in which the projective module is actually free. We discuss the properties of projective multiresolution analyses, including the frames which they provide for L²(ⁿ). Then we show how to construct examples for the case of any diagonal 2 × 2 dilation matrix with integer entries, with initial module specified to be any fixed finitely generated projective C(T²)-module. We compute the isomorphism classes of the corresponding wavelet modules.     

Reactivity and chemical synthesis of L-pyrrolysine- the 22(nd) genetically encoded amino acid

L-pyrrolysine, the 22(nd) genetically encoded amino acid, was previously deduced to be (4R, 5R)-4-substituted-pyrroline-5-carboxylate attached to the epsilon-nitrogen of lysine based on the crystal structure of the M. barkeri monomethylamine methyltransferase (MtmB). To confirm L-pyrrolysine's identity, structures of MtmB have been determined following treatment with hydroxylamine, N-methylhydroxylamine, or dithionite. Analysis of these structures has provided additional support for the presence of the pyrroline ring and, together with previous mass spectroscopy data, has led us to assign the C(4)-substituent to a methyl group. Based on this assignment, synthetic L-pyrrolysine was prepared by chemical methods. Detailed study of this chemically synthesized L-pyrrolysine has allowed us to characterize its physical properties, to study its chemical stability, and to elucidate the role of its C(4) substituent. Future applications of this synthetic L-pyrrolysine include its in vivo incorporation into recombinant proteins.     

Preparation and structural characterisation of methoxybis(trimethylsilyl)silyl potassium and its condensation product

Depending on the conditions the reaction of tris(trimethylsilyl)methoxysilane (1) with potassium tert-butoxide either in benzene and in the presence of 18-crown-6 or in THF gives either the crown ether adduct of potassium-methoxybis(trimethylsilyl)silane (2), or 2-methoxytetrakis(trimethylsilyl)disilanyl potassium (3).     

Synthesis and characterization of model compounds of the lysine tyrosyl quinone cofactor of lysyl oxidase

4-n-Butylamino-5-ethyl-1,2-benzoquinone (1(ox)) has been synthesized as a model compound for the LTQ (lysine tyrosyl quinone) cofactor of lysyl oxidase (LOX). At pH 7, 1(ox) has a lambda(max) at 504 nm and exists as a neutral o-quinone in contrast to a TPQ (2,4,5-trihydroxyphenylalanine quinone) model compound, 4, which is a resonance-stabilized monoanion. Despite these structural differences 1(ox) and 4 have the same redox potential (ca. -180 mV vs SCE). The structure of the phenylhydrazine adduct of 1(ox) (2) is reported, and 2D NMR spectroscopy has been used to show that the position of nucleophilic addition is at C(1). UV-vis spectroscopic pH titration of phenylhydrazine adducts of 1(ox) and 4, 2, and 11, respectively, reveals a similar red shift in lambda(max) at alkaline pH with the same pK(a) (approximately 11.8). In contrast, the red shift in lambda(max) at acidic pH conditions yields different pK(a) values (2.12 for 2 vs -0.28 for 11), providing a means to distinguish LTQ from TPQ. Reactions between in situ generated 4-ethyl-1,2-benzoquinone and primary amines give a mixture of products, indicating that the protein environment must play an essential role in LTQ biogenesis by directing the nucleophilic addition of the epsilon-amino group of a lysine residue to the C(4) position of a putative dopaquinone intermediate. Characterization of a 1,6-adduct between an o-quinone and butylamine (3-n-butylamino-5-ethyl-1,2-benzoquinone, 13) confirms the assignment of LTQ as a 1,4-addition product.     

A Conversation with Lee Alvin DuBridge - Part II

Physicist Lee A. DuBridge became president of the California Institute of Technology in 1946. In this interview he recalls his dealings at Caltech with Linus Pauling; his memories of George W. Beadle, Theodore von Kármán, and J. Robert Oppenheimer; the military Vista Project at Caltech; and the difficulties surrounding the deportation of Hsue-Shen Tsien, Caltech's Goddard Professor of Jet Propulsion.