Synthese und Bestimmung der absoluten Konfiguration von Norpyrenophorin, Pyrenophorin und Vermiculin

Abstract

Aus den Alkylhalogeniden 4,5 und 6 werden in wenigen Schritten die Hydroxysauren 8,lOb bzw. 15b (allgemeine Formel E) mit 1,3-Dithian-geschiitzten Ketogruppen synthetisiert. 10b und 15b erhalt man in enantiomerenreiner Form, wenn man von den aus Hydroxybuttersaure oder Apfelsaure leicht erhaltlichen chiralen Vorlaufern 5 bzw. 6 ausgeht. Von den drei gebrauchlichen Methoden der Makrocyclisierung (Dipyridyldisul fid/Triphenylphosphin, Azodicarbonsaure-diethylester/Triphenylphosphin und 2-Halogenpyridiniumsalz) uberfuhrt nur die Reaktion mit Azodicarbonsaurediester/Triphenylphosphin nach Mitsunobu die schwefelhaltigen Hydroxysauren in die Diolide 16 -18, deren Thioacetalgruppen mit QuecksiIber(I1)-oxid/Bortrifluorid hydrolytisch abgespalten werden. Dabei entstehen die im Titel genannten Makrolide 1 -3, Pyrenophorin (2) und Vermiculin (3) in optisch aktiver Form. Es wird durch Modellversuche [Gleichungen (1) -(3)] gezeigt, daB bei der dimerisierenden Veresterung mit Azodicarbonsaurediester/Triphenylphosphin Konfigurationsumkehr am alkoholischen Chiralitatszentrum eintritt. Dadurch sind die in Schema 1 zusammengefafiten Synthesen von Pyrenophorin (R, R-2) und Vermiculin (S, 9 3 ) Bestimmungen der bisher unbekannten absoluten Konfigurationen dieser Naturstoffe. Die Gesamtausbeuten vom Alkylierungsmittel bis zu den Dioliden (4-1, 5-2 und 6-3) liegen bei 17, 27 bzw. 8%. -Eine Untersuchung des antimikrobiellen Wirkungsspektrums zeigt keinen Unterschied zwischen (+)-und (-)-Vermiculin oder (-)-und (+)-Pyrenophorin; die physiologische Wirksamkeit des am Diolidring unsubstituierten, achiralen Norpyrenophorins ist annahernd gleich der des Pyrenophorins. Syntheses and Determinations of the Absolute Configurations of Norpyrenophorin, Pyrenophorin, and VermicuIine1.*)The hydroxy acids 8, lob, and 15b (see general formula E) with 1,3-dithiane-protected keto groups are synthesized in a few steps from the haloalkanes 4, 5, and 6, respectively. The chiral acids 10b and 15b are obtained in optically pure form if the starting materials 5 and 6, respective-*) Korrespondenz bitte an diesen Autor richten.Norpyrenophorin, Pyrenophorin und Vermiculin 2045 ly, are synthesized from 3-hydroxybutyric acid and malic acid. Of the three most frequently used methods of macrocyclization (dipyridyl disulfide/triphenylphosphine, diethyl azodicarboxylate/ triphenylphosphine, and 2-halopyridinium salt), only Mitsunobu's reaction with diethyl azodicarboxylate/triphenylphosphine works with the sulfur-containing hydroxy acids. The thioketal groups in the resulting diolides 16 -18 are hydrolyzed with mercuric oxide/boron trifluoride to give the macrolides 1 -3, pyrenophorin (2) and vermiculine (3) in a single enantiomeric form. Model studies outlined in equations (1) -(3) show that dimerizing esterification with diethyl azodicarboxylate/triphenylphosphine takes place with inversion at the center of chirality. Thus, the present syntheses of pyrenophorin (R,R-2) and vermiculine (S,S-3), see flowsheet in Scheme 1, also constitute assignments of the hitherto u...

Diversity of Antimicrobial Pyrenophorol Derivatives from an Endophytic Fungus, Phoma sp.

“…The isolation of twelve different derivatives by isolation or chemical transformations and comparison of their data enabled the complete assignment of all signals in the 1 H and 13 C NMR spectra of the pyrenophorol family that have not previously been completely reported. [20][21][22][23][24][36][37][38][39][40][41][42] Experimental Section General Experimental Procedures: For microbiological methods and culture conditions, see refs.…”

“….1 mg, 83 %). [20][21][22][23][36][37][38][39][40][41][42] Synthesis of 4,4Ј-Diacetylpyrenophorol (11) by Acetylation of Pyrenophorol (1): To a solution of 1 (9.0 mg) in dry pyridine (0.5 mL) were added 2 drops of Ac 2 O. The mixture was kept at room temperature for 16 h to afford, after usual workup, 11 [4] quantitatively ( …”

High‐Yield Synthesis of 20‐, 24‐, and 28‐Membered Macropentolide, ‐hexolide, and ‐heptolide, Respectively, from (R)‐ or (S)‐3‐hydroxybutanoic acid under Yamaguchi's macrolactonization conditions

“…With the exception of conglobatine [3], these fungal metabolites have antibiotic activity, in some cases even irrespective of their sense of chirality or substitution pattern. Thus, both enantiomers of pyrenophorine (A, R' = CH,, FG = 5,13-dioxo) and the achiral norpyrenophorine (A, R' = H, FG = 5,13-dioxo) all exhibit very similar activity towards a number of microorganisms [4]. In the course of our work on syntheses of these compounds and as a consequence of our interest in 3-hydroxybutanoic acid as a chiral building block (for reviews, see [I] [7]), it occurred to us that the tetramer B of this acid might also be antibiotic').…”

Oxidation of α,β‐Unsaturated Esters and Lactones with Selenium Dioxide to γ‐Oxo or γ‐Hydroxy Derivatives; Synthesis of (±)‐A 26771 B and Norpyrenophorin

“…They are well-defined cyclic compounds with a large number of ring members (52 to 104). They belong to the class of chiral yet highly symmetrical compounds (point group symmetry C,,, n = 4 , 6,8), for which only a few examples are known.lhl As crown ethers, they are potential host molecules. On account of their chirality, they are expected to be enantioselective, like the compounds 4 and 5.I'I It is therefore advantageous that their sense of chirality, or absolute configuration, is known.…”