Stereoselective total syntheses and reassignment of stereochemistry of the freshwater cyanobacterial hepatotoxins cylindrospermopsin and 7-epicylindrospermopsin

A stereoselective total synthesis of the structure 1 proposed for the freshwater cyanobacterial heptatotoxin cylindrospermopsin has been accomplished in approximately 30 operations starting from commercially available 4-methoxypyridine. Utilizing methodology developed by Comins, the tetrasubstituted piperidine A-ring unit of the hepatotoxin was efficiently constructed. The two remaining stereocenters in the natural product were then set by a stereospecific intramolecular N-sulfinylurea Diels-Alder cyclization/Grignard ring opening/allylic sulfoxide [2,3]-sigmatropic rearrangement sequence previously developed in these laboratories, leading to key intermediate 29. The stereochemical assignment of alcohol 29, which contains all six of the stereogenic centers of the natural product, was confirmed by an X-ray crystal structure determination of a derivative. Installation of the D-ring uracil moiety was effected by using our new methodology developed for this purpose, and construction of the C-ring guanidine completed the total synthesis of racemic structure 1. However, the (1)H NMR data for this compound do not match that of cylindrospermopsin, but instead agree with the data reported for 7-epicylindrospermopsin, a minor toxic metabolite that co-occurs with cylindrospermopsin. Therefore, we propose a revision of the stereochemical assignments of these natural products such that cylindrospermopsin is now represented as structure 2 and 7-epicylindrospermopsin is 1. This reassignment was further confirmed by Mitsunobu inversion of the C-7 alcohol 51 to epimer 52, and conversion of this compound to tetracyclic diol 57, which has previously been transformed to cylindrospermopsin (2).     

ON THE LUMINESCENCE OF ESTROGENS

Abstract —The absorption, fluorescence, and phosphorescence of a series of estrogens is reported. The behavior of estrogens without a keto-group is compared with that of the isolated phenylic, phenolic and naphtholic chromophores. In the latter two, attachment to the steroidal frame is inconsequential as regards their luminescent behavior. In all keto-estrogens with the exception of equilenin there is a very strong transfer of excitation energy from the A ring chromophore to the keto group. The fluorescence of 6-keto-estradiol, which has a conjugated aromatic carbonyl chromophore, is apparently due to the rigidity of the steroid frame and exhibits a rather perculiar excitation spectrum.     

Synthesis of β-tosylethylhydrazine and its use in preparation of N-protected pyrazoles and 5-aminopyrazoles

β-Tosylethylhydrazine (6) can be prepared efficiently in one step from commercially available p-tolyl vinyl sulfone (7) and hydrazine hydrate. This hydrazine reacts with both 1,3-diketones and conjugated ynones in glacial acetic acid to provide a variety of N-tosylethyl-protected (TSE) pyrazoles in good yields. The TSE group can be removed from the pyrazoles using potassium t-butoxide in THF at −30 °C-rt. In addition, hydrazine 6 condenses with β-ketonitriles and β-aminoacrylonitriles to afford 5-aminopyrazoles, which can be deprotected by brief treatment with NaOEt in EtOH/DMSO at 45 °C.     

On finite groups with a sylowp-subgroup of type (m,n)

A finitep-groupP is of type (m, n) ifP has nilpotency classm-1,P/P'≌Z _p ⁿ ×Z _p ⁿ and all the lower central factorsK _i (P)/K _i+1 (P) are cyclic of orderp ⁿ . Our main result on finite groups with a Sylowp-subgroup of type (m, n) is (Theorem 4.1): Let G be a finite group with a Sylow p-subgroup P of type (m, n), n≧2 p≧3, m≧(n+5)(p?1)+1. For H≦G denote \(\bar H = HO_{p'} (G)/O_{p'} (G)\) . If O_p (G) is not cyclic and P'₁ ≠ 1, then \(\bar P \Delta \bar G\) and \(\bar G = \bar P \cdot \bar T\) is a semidirect product of \(\bar P\) and \(\bar T\) , where \(\bar T\) is cyclic of order t, t|p-1. Here P₁ is the subgroup defined in section 0. This theorem easily yields that under its assumptionsN _G (P)/O ^P (N _G (P))≌G/O ^P (G), it gives information on the conjugacy pattern ofp-elements ofG and gives information on the structure ofp-local subgroups ofG (Theorems 4.2, 4.3 and 4.4).     

An Alternative Procedure for the Aluminum-Mediated Conversion of Esters to Amides

A convenient method has been developed for directly converting esters to amides using reagents derived from the reaction of trimethylaluminum with ammonium chloride, methylamine hydrochloride or dimethylamine hydrochloride.     

Further studies of intramolecular Michael reactions of nitrosoalkenes for construction of functionalized bridged ring systems

A wide variety of stabilized carbanions have been found to participate as nucleophiles in intramolecular Michael-type conjugate additions to in situ generated nitrosoalkenes to form bridged carbocyclic systems. The vinylnitroso platforms for these cyclizations have been prepared via two key steps involving ring-closing metathesis of vinyl chlorides and regioselective conversion of vinyl chlorides to α-chloroketones with sodium hypochlorite in glacial acetic acid/acetone. An alternative approach to preparation of some cyclization substrates has involved use of more reactive enol ethers as precursors to the requisite α-chloroketones. A sulfonamide anion has also been found to be an effective nucleophile in this type of reaction, leading to formation of a 6-azabicyclo[3.2.1]octane.     

345 GHZ PROTOTYPE SIS MIXER WITH INTEGRATED MMIC LNA

We report on heterodyne measurements at submillimeter wavelengths using a receiver with a Superconductor-Insulator-Superconductor (SIS) mixer device and a Microwave Monolithic Integrated Circuit (MMIC) cryogenic low noise amplifier (LNA) module integrated into the same block. The mixer characterization presented in this work demonstrates the feasibility of operating a MMIC LNA in close proximity to the SIS device without penalty in mixer performance due to heating effects. Verification of this functionality is crucial for the ongoing development of SuperCam, a 64-pixel focal plane array receiver consisting of eight, 1 × 8 integrated mixer/LNA modules. The test setup included a mixer block modified to accept a MMIC amplifier. Our tests show that the LNA can be operated over a broad range of V_drain voltages from 0.40–1.40 V, corresponding to dissipative powers of 2.6–29 mW. We observe no significant effect on the measured uncorrected receiver noise temperatures in the 345 GHz band.     

A unified derivation for fast estimation algorithms by the conjugate direction method

Fast estimation algorithms inspired by the classical method of Levinson have been developed in the areas of time series analysis, system identification, and signal processing. This paper provides a unified derivation for the Levinson-Durbin-Whittle-Wiggins-Robinson, fast recursive least squares (RLS), ladder (or lattice), and fast Cholesky algorithms as special cases of the conjugate direction method (CDM). This gives a novel derivation and interpretation for all these methods.