Synthesis of the C(43)-C(67) fragment of amphidinol 3

[reaction: see text] A synthesis of the C(43)-C(67) fragment of amphidinol 3 (AM3) has been accomplished by a route that features the use of a double allylboration reaction for synthesis of 1,5-diol 4b, which serves as a precursor to dihydropyran 11.     

Synthesis of 2,6-trans-disubstituted 5,6-dihydropyrans from (Z)-1,5-syn-endiols

Certain (Z)-1,5-syn-diols 2 may be converted into 2,6-trans-5,6-dihydropyrans by using phosphonium salt 4 or phosphorane 5 as dehydrating agents. A more general four step procedure converts the (Z)-1,5-syn-endiols into enantiomeric dihydropyrans ent-3 via regioselective silylation of the allylic alcohol unit followed by mesylate formation and base-promoted nucleophilic displacement.     

Theoretical study of the metastable peaks corresponding to the rotational predissociation of the CH4+ and CD4+ ions

Semiclassical calculations on diatomic type models are presented in order to account for the kinetic energy released in the metastable dissociation of the CH₄⁺ and CD₄⁺ ions; the discrete structure of the metastable peaks is considered.     

Nebenreaktionen der Chloraminherstellung

Subreactions in the Chloramine Preparation. In the preparation of chloramine from solutions of ammonia and sodium hypochlorite there is considerable overchlorination, resulting in the formation and subsequent decomposition of dichloramine. Nitrogen, chloride ion, and hypochlorite ion are formed in the decomposition of dichloramine; in the presence of certain organic compounds the products of chlorination via radicals are observed. Chloramine is obtained in over 90% yield by neutralizing the alkali formed in the reaction of ammonia with hypochlorite. Etheral solutions of dichloramine are prepared from chloramine solutions by treatment with phosphate buffer.     

The rotational predissociation of the CH4+ and CD4+ ions

The metastable transitions producing CH₃³/CH₄ and CD₃⁺/CD₄ have been investigated by means of translational spectroscopy. For the first time structures are observed in a metastable peak corresponding to the dissociation of a polyatomic ion. They are interpreted by tunneling through a rotational barrier from discrete quasi-bound states. Kinetic energy releases have been measured.     

Laser-induced photodissociation of He+2

The momentum distributions of He⁺ fragments from photodissociation of He⁺₂ ions have been recorded in a crossed-beams experiment. The discrete values of the kinetic energy releases can be predicted from the vibrational spacings in the ground state of the primary ions.     

Design, synthesis, and reactivity of 1-hydrazinodienes for use in organic synthesis

A new 1-hydrazinodiene (1) has been developed and utilized in Lewis acid catalyzed, intermolecular Diels-Alder reactions with various electron-deficient alkenes. The hydrazine can then be deprotected, and a molecule of methanesulfinic acid is eliminated to provide a putative diazene intermediate (4), which then spontaneously undergoes a suprafacial 1,5-sigmatropic shift to yield stereochemically complex cyclohexenes. This method has been applied to the synthesis of a constitutionally and stereochemically complex decalin derivative.     

Synthesis of the C(1)-C(25) fragment of amphidinol 3: application of the double-allylboration reaction for synthesis of 1,5-diols

[structure: see text] A synthesis of the C(1)-C(25) fragment of amphidinol 3 is described. The synthesis features two applications of double allylboration reaction methodology for the highly stereoselective synthesis of 1,5-diol units in the C(1)-C(15) segment.     

Chimeric protein probes for C5a receptors through fusion of the anaphylatoxin C5a core region with a small-molecule antagonist

Blockade of the interaction of anaphylatoxin C5a with its receptor C5aR1 has been actively studied as a potential treatment for many inflammatory diseases; but current C5a antagonists exhibit inadequate potency and poor species cross-reactivity, and novel biochemical tools are needed to investigate whether the core region of C5a contains important interaction epitopes that can explain these limitations. Herein, we report the development of chimeric protein C5a probes containing both the complete core region of rat or human C5a, and the small-molecule antagonist PMX53-1. These probes were chemically synthesized through hydrazide-based native chemical ligation of a linear peptide hydrazide with the requisite cyclopeptidic antagonist, both of which were made by solid-phase synthesis. Quasi-racemic X-ray crystallography established that attachment of PMX53-1 did not affect the structure of the core region of C5a. Subsequent C5aR1 activity assays demonstrated the probes can provide valuable insights into the development of C5a antagonists; for example, they exhibited significantly better binding affinity and much improved species cross-reactivity than PMX53-1, supporting the notion that the effect of some epitopes outside the C-terminus of C5a should be taken into consideration when designing better C5a antagonists. Surprisingly, the core region of C5a was found to partially agonize C5aR1, suggesting the presence of more than one agonistic interaction in the binding of C5a to C5aR1. This study exemplifies the value of chemical protein synthesis in developing novel receptor probes for drug discovery research.