Total synthesis of (-)-reveromycin B

[structure: see text] The total synthesis of the epidermal growth factor inhibitor reveromycin B (2) is described. A novel, convergent, and stereoselective reaction sequence was utilized to construct the 5,6-spiroketal system 10 which was converted into the natural product 2 by a 16-step sequence.     

Determination of ultramicro amounts of sulphate as methylene blue—II The reduction

Sulphate may be determined spectrophotometrically as methylene blue after reduction to sulphide, which is allowed to react with p-aminodimethylaniline and ferric iron to form the dye. A previous paper¹ dealt with the colour reaction; this paper deals with the reduction.

A method for the reduction of sulphate to sulphide by hydriodic and hypophosphorous acids in acetic acid solution is proposed. It is founded on an investigation of the following variables: composition of the reducing reagent, composition of the carrier gas and gas-washing liquid, temperature at reduction, and time. The yield of the reduction is found to be 100% within the experimental errors. The standard deviation of a single determination of 100 μg S or 2 μg S is found to be 0.14 μg S or 0.05 μg S, respectively. Some interferences in connection with the application of the method for certain purposes are discussed.     

TheC ℓ Bailey transform and Bailey lemma

TheC _? nonterminating C_? summation theorem is derived by appropriately specializing Gustafson's₆ψ₆ summation theorem for bilateral basic hypergeometric series very well-poised on symplecticC _? groups. From this, the terminating₆?₅ and, hence, terminating₄?₃ summation theorem is obtained. A suitably modified₄?₃ is then used to derive theC _? generalization of the Bailey transform. The transform is then interpreted as a matrix inversion result for two infinite, lower-triangular matrices. This result is used to motivate the definition of theC _? Bailey pair. TheC _? generalization of Bailey's lemma is then proved. This result is inverted, and the concept of the bilateral Bailey chain is discussed. TheC _? Bailey lemma is then used to obtain a connection coefficient result for generalC _? littleq-Jacobi polynomials. All of this work is a natural extension of the unitaryA _?, or equivalentlyU(?+1), case. The classical case, corresponding toA ₁ or equivalentlyU(2), contains an immense amount of the theory and application of one-variable basic hypergeometric series, including elegant proofs of the Rogers-Ramanujan-Schur identities. TheC _? nonterminating₆?₅ summation theorem is also used to recover C. Krattenthaler's multivariable summation which he utilized in deriving his refinement of the Bender-Knuth and MacMahon generating functions for certain sets of plane partitions.     

Total synthesis of the epidermal growth factor inhibitor (-)-reveromycin B

The total synthesis of the epidermal growth factor inhibitor reveromycin B (2) in 25 linear steps from chiral methylene pyran 13 is described. The key steps involved an inverse electron demand hetero-Diels-Alder reaction between dienophile 13 and diene 12 to construct the 6,6-spiroketal 11 which upon oxidation with dimethyldioxirane and acid catalyzed rearrangement gave the 5,6-spiroketal aldehyde 9. Lithium acetylide addition followed by oxidation/reduction and protective group manipulation provided the reveromycin B spiroketal core 8 which was converted into the reveromycin A (1) derivative 6 in order to confirm the stereochemistry of the spiroketal segment. Introduction of the C1-C10 side chain began with sequential Wittig reactions to form the C8-C9 and C7-C6 bonds, and a tin mediated asymmetric aldol reaction installed the C4 and C5 stereocenters. The final key steps to the target molecule 2 involved a Stille coupling to introduce the C21-C22 bond, succinoylation, selective deprotection, oxidation, and Wittig condensation to form the final C2-C3 bond. Deprotection was effected by TBAF in DMF to afford reveromycin B (2) in 72% yield.     

Determination of ultramicro amounts of sulphate as methylene blue—I The colour reaction

Sulphate may be determined spectrophotometrically as methylene blue after reduction to sulphide, which is allowed to react with p-aminodimethylanuine and ferric iron to form the dye. This paper deals with the colour reaction.

The standard method for the colour development proposed is founded on an investigation of the following variables: hydrogen sulphide losses, acidity at reaction and measurement, reagent concentrations, temperature at reaction and measurement, concentration of traces of heavy metals, time, and air-oxidation. Previously found deviations from Beer's law are confirmed and discussed. The yield of the reaction is determined.     

Cyanid

Ohne Zusammenfassung