A. Tuinman

The structure of cyanoginosin-LA, a cyclic heptapeptide toxin from the cyanobacterium Microcystis aeruginosa

The structure of cyanoginosin-LA (previously referred to by us as toxin BE-4) is cyclo(-D-Ala-L-Leu-erythro-β-methyl-D-isoAsp-L-Ala-Adda-D-Glu-N-methyldehydroAla)(17a), where Adda refers to the novel β-amino acid residue of 3-amino-9-methoxy-2,6,8-trimethyl-10-phenyldeca-4,6-dienoic acid (11). The connectivity of Adda is deduced from 1H- and 13C-n.m.r. data, but the stereochemistry at carbons 2,3,8, and 9 remains unknown. The residue sequence is derived from the mass spectra of cyclic and linear derivatives of the toxin. A new nomenclature for the related toxins of Microcystis aeruginosa is discussed.

A partial structure for the toxin BE-4 from the blue-green algae, Microcystis aeruginosa

The amino acid sequence of a peptide fragment of a peptide toxin isolated from the blue-green algae, Microcystis aeruginosa, is D-Ala-L Leu-erythro-β-methyl-D-isoAsp-L Ala-Baa-D-Glu, where Baa is a novel β-amino acid; the toxin is monocyclic, and the position of an N-methyldehydroalanine residue has been tentatively established.

An efficient method for converting 17-oxo- into 17-acetyl steroids

Abstract A study of certain reaction parameters of the recently described procedure for converting ketones to the corresponding carbonitriles using tosylmethyl isocyanide, has led to a modified method suitable for the efficient synthesis of 17-cyanosteroids. These products readily undergo methylation to give the corresponding 17-acetyl compounds. This two-step conversion of steroidal 17- to 20-ketones proceeds in excellent overall yields, and constitutes a particularly mild and simple alternative method to those hitherto used for this purpose.

The isolation, structure, and absolute configuration of the mycotoxin, rhizonin A, a novel cyclic heptapeptide containing N-methyl-3-(3-furyl)alanine, produced by Rhizopus microsporus

Rhizonin A, the main mycotoxin from Rhizopus microsporus, is a cyclic heptapeptide containing valine, allo-isoleucine, leucine, N-methylalanine, N-methyl-3-(3-furyl)alanine (2 : 1 : 1 : 1 : 2), its amino-acid sequence having been established by mass spectrometry; X-ray crystallography verified the structure of rhizonin A and afforded its conformation and relative configuration, and its absolute configuration was obtained from high performance liquid chromatographic studies of the dansyl-derivatised amino-acids.

Steroidal analogues of unnatural configuration—VII : Total synthesis of 17β-hydroxy-9-methyl-9β, 10α-oestr-4-en-3-one, a novel retrotestosterone isomer☆☆☆

Abstract Conjugate methylation of 17β-hydroxy-des- a -oestr-9-en-5-one ( 1 ) and the derived 4,5-seco-steroid ( 6b ) afforded the respective 9β-methyl compounds. Base-catalysed alkylation of 17β-hydroxy-9-methyl-des- a -9/gb-oestran-5-one ( 3a ) resulted in attack at C(6); this result was used to prepare the anthrasteroid ( 5 ). Ring closure of the 9β-methyl-4,5-seco-steroid ( 8 ) derived from 6b afforded 17β-hydroxy-9-methyl-9β,10α-oestr-4-en-3-one ( 9a ). Conjugate methylation of 17β-hydroxyoestra-4,9-dien-3-one ( 11 ) resulted in 1,4-addition to the dienone system.

Steroidal analogues of unnatural configuration—X : Synthesis of 9-methyl-19-nor-9β,10α-progesterone☆

Abstract The reaction of 3,3-ethylenedioxy-9-methyl-9β-oestr-5(10)-en-17-one (4) with tosylmethyl isocyanide and base afforded the 17β- and 17α-carbonitriles (5 and 6). Treatment of the 17β-epimer (5) with methyl lithium gave, after hydrolysis, 9-methyl-19-nor-9β-pregn-5(10)-ene-3,20-dione (8). The same reaction sequence employed on 3,3; 5,5-bisethylenedioxy-9-methyl-4,5-seco-9β,10α-oestr-17-one (12), with subsequent cyclization, yielded the 5β-hydroxy-3,20-diketones (17 and 18) as well as 9-methyl-19-nor-9β,10α-progesterone (19) and its 17α-epimer (20).

Steroidal analogues of unnatural configuration—171 : Conformational analysis of 4,4,14α-trimethyl-19(10→9β) ABEo-5α,10α-pregnane-6,11-dione☆

Abstract The cis-transoid-cis steroidal analogue 1 was predicted by force field calculations to have non-chair rings B and C . X-ray structure determination confirmed this result.The conformational effects of various salient features of 1 have been investigated by force field methods.

Steroidal analogues of unnatural configuration. Part 14. Conformational analysis of 4,4,14α-trimethyl-19(10→9β)abeo-5β,10α-pregnane-6,11-diols by X-ray crystallography and force-field calculations

The X-ray structures of the 6α,11β-(6), 6β,11β-(7), and 6β,11α-diols (8) have been determined, and their conformations shown to be predicted accurately by the force-field method. The 6β,11α-diol (8) favours a flattener all-chair conformation, whereas rings B and C of (6) and (7) adopt non-chair conformations in response to served α-face interactions. The detailed conformational analysis of the 6,11-diols is discussed in terms of puckeinge parameters, and the steric energies of different conformers are compared. The 6α,11α-diol (9) for which X-ray crystallographic data could not be obtained is predicted by force-field calculations to prefer non-chair conformations of rings B and C, in apparent contradiction of spectroscopic findings.

Intramolecular condensation of steroidal α-acetoxy-ketones

Intramolecular condensation of tertiary α-acetoxy-ketones in the cholestane series takes place in the presence of lithium di-isopropylamide to give products derived from nucleophilic attack of an ester enolate anion upon the adjacent oxo-group. When the acetoxy-group is axial, condensation proceeds rapidly at –78 °C to give the corresponding β-hydroxy-γ-lactone, but when it is equatorial the reaction is less efficient, and is attended by dehydration of the primary product.

Steroidal analogues of unnatural configuration—IX: NMR spectroscopy and conformational analysis of 9β,10α- and 10α-pregnanes derived from the cucurbitacins

Abstract NMR spectra of 78 cucurbitacin derivatives were analysed for evidence of conformational aberrations in the c-ring, and differences were found in the 9β-Me, 9β-H and 9α-H series. Evidence in support of postulated ring deformations was obtained from solvent-dependent and lanthanide shift spectra of selected model substances.