The structure and absolute configuration of pseurotin (1), a new metabolite, isolated from culture filtrates of Pseudeurotium ovalis STOLK (Ascomycetes), has been shown to be 2‐[1′(S), 2′ (S)‐dihydroxhex‐3′‐ene‐yl]‐3‐methyl‐8(S)‐methoxy‐8‐benzoyl‐9(R)‐hydroxy‐(5S)‐1‐oxa‐7‐aza‐spiro[4.4]non‐2‐ene‐4, 6‐dione (1), by spectral data and chemical transformations, and by X‐ray analysis of its dibromo derivative 2 [1].

ZUSAMMENFASSUNG 1235 4,5,6-Trimethoxy-N, N-dimethyl-tryptamin (XI) und zwei dem Mescalin nahestehende Verbindungen, fi-(3,4,5-Trimethoxyphenoxy)-athyl-amin (VI) und ,4,5-Trimethoxyphenoxy)-athyl-dimethylamin (III), wurden synthetisiert. Keine der drei Substanzen zeigte in vorlaufigen Humanversuchen psychotrope Aktivitat. Vor etwa 28 Jahren haben OXFORD et ~1 .~) aus dem Kulturfiltrat von Penicillium brefeldianum DODGE die Fulvinsaure (I) z, 3, isoliert. Der gleiche Pilz produziert auch Grise~fulvin~). Bei der Untersuchung eines Stammes (S 464) dieses Pilzes haben wir als Hauptprodukt Palitantin (11) 4, gefunden. In kleinerer Menge konnten wir das mit Palitantin eng verwandte Frequentin (111) 5, 6 , sowie zwei neue Stoffwechselprodukte isolieren, die wir Brefeldin A und Brefeldin B nennen. Fulvinsaure und Griseofulvin liessen sich bisher in keiner unserer Ziichtungen, die unter den verschiedensten Bedingungen durchgefiihrt wurden, nachweisen. Dagegen konnten wir Brefeldin A auch aus dem Kulturfiltrat eines weiteren Penicillium-Stammes (S 498) als Hauptmetabolit gewinnen. Als Nebenprodukt erhielten wir aus diesem Stamme noch 1-0-Stearylglycerin (cc-Monostearin)

A series of cytostatically active metabolites have been isolated from microorganisms in recent years. These compounds, which are chemically closely related, are of a new structural type. A highly substituted hydrogenated isoindolone unit is fused to an 11-to 14-membered macrocycle. The large ring may be carbocyclic or heterocyclic (lactone or carbonic diester). The absolute configurations of two cytochalasans (phomin and a cytochalasin D derivative) have been established by X-ray analysis. The biogenesis of phomin (cytochalasin B) is broadly known, and it is probable that all cytochalasans have a common biogenetic scheme. All the compounds of this class have a more or less pronounced specifically cytostatic action.

SummaryPig liver esterase-(PLE) catalyzed hydrolysis of dimethyl esters of symmetrical dicarboxylic acids, including meso-diacids, cis-1,2-cycloalkanedicarboxylic acids, and diacids with a prochiral center, was studied with 14 substrates. The products of these stereoselective hydrolyses are chiral monoesters of dicarboxylic acids, with an enantiomeric excess (e.e.) from 10% to 100%. Some of these optically active monoesters are valuable synthons in natural products synthesis.An additivity pattern of a-and /3-substituents with the glutaric esters on the stereoselectivity of enzymatic hydrolysis was observed. Analysis of the experimental results leads to a model of enzyme stereoselectivity of diester hydrolysis in which the substitution pattern at a-and a-C-atoms is found to determine the absolute configuration of the resulting monoester.The control of absolute stereochemistry is of fundamental importance for natural product synthesis [l]. Although a plethora of chemical methods has been developed for the construction of optically active compounds [2], the unique opportunity provided by enzymes as catalysts in asymmetric synthesis is being increasingly exploited [3].It is theoretically possible, by utilizing the enantioselectivity of enzymes towards meso-compounds and compounds with a prochiral center to transform the total amount of starting material into a target molecule. The classical example of this kind of transformation represents the synthesis of (R)-mevalonolactone using the high selectivity provided by pig liver esterase (PLE) towards dimethyl 3-hydroxy-3-methylglutarate [4]. From a preparative standpoint it is important to note that by appropriate manipulation of the functional groups (S)-mevalonolactone can also be synthesized.We can envisage that by using enzymes which possess low substrate selectivity but which at the same time catalyze reactions with a high degree of stereoselectivity, a large number of new chiral synthons can be provided. a-Chymotrypsin [5], horse liver alcohol dehydrogenase [6], PLE [7], and some other esterases from different microorganisms [8] have already been used to provide chiral synthons of highest optical purity for the synthesis of natural products.

The isolation and structure elucidation of the new spirostaphylotrichins B (2), C and D (3/4), F (5), Q (6), and R (7) are described. Compounds 2 and 3 are artefacts formed during the isolation of the metabolites from the cultures. The absolute configuration of spirostaphylotrichin A (1) has been determined by CD spectroscopy.Introduction. -Spirostaphylotrichin A (1) is a secondary metabolite which has been isolated by Peter and Auden [ 11 from cultures of the fungus Staphylotrichurn coccosporum. Its structure and relative configuration were established by an X-ray analysis. The compound represents a novel structural type of natural products. In the course of our investigations on the biosynthesis of 1 [2], we have isolated six new metabolites, named

Incorporation of [1‐13C]‐, [2‐13C]‐ and [1,2‐13C2]‐acetate, [1‐13C]‐propionate, [13C‐CH3]‐L‐methionine and [3‐14C]‐DL‐tryptophan into chaetoglobosin A (1) and 19‐O‐acetylchaetoglobosin A (2) by Chaetomium globosum demonstrated that the building blocks of 1 and 2 are 9 and 10 units of acetate/malonate respectively, 3 units of methionine and 1 unit of tryptophan. Propionate is incorporated indirectly after several biological transformations. Using [2‐13C, 2‐2H3]‐acetate as precursor, the starter unit of the polyketide‐chain was identified. Experiments which [13C, 2H3‐CH3‐L‐methionine demonstrated that the three C‐methylations occur with retention of all three H‐atoms of the methyl group. Incorporation experiments with various 14C‐ and 3H‐labelled tryphtophan samples and with [2‐2H]‐ and [2‐15N]‐L‐tryptophan showed that the amino acid is incorporated intact with retention of both the α‐H‐ and the α‐N‐atom. On the basis of these results a more detailed general scheme of the cytochalasan biogenesis is proposed.

A systematic nomenclature based on the generic name cytochalasan is proposed for the cytochalasins, phomins, and zygosporins.

No abstract