Enantioselektive Totalsynthese der Terreumole A und C aus dem Pilz Tricholoma terreum

Abstract

Erstmals gelang die enantioselektive Totalsynthese der cytotoxischenM eroterpenoide Terreumol Au nd Ca us dem Gemeinen Erd-Ritterling Tricholoma terreum. Schlüsselschritt ist der Aufbau des zehngliedrigen Rings durchO lefinmetathese zur trisubstituierten Z-Doppelbindung des [8.4.0]-Bicyclus,d ie nur in Abwesenheit freier Hydroxygruppen gelang.( À)-Terreumol Cw urde vollständig diastereoselektiv in das Bisepoxid( À)-Terreumol Aü berführt, das somit ausgehend von 2-Brom-3,4-dimethoxybenzaldehyd in 14 Stufen und einer Gesamtausbeute von 23 %erhalten wurde. Eine Rçntgenstrukturanalyse des p-Benzochinon-Analogons von (À)-Terreumol Abestätigt die absolute Konfiguration der Naturstoffe.Schema 4. Ringschlussmetathesezu(À)-Terreumol C(2). IBX = o-Iodoxybenzoesäure.Schema 5. Oxidation von (À)-Terreumol C(2)zu(À)-Terreumol A(1) und zum p-Benzochinon 25 mit Molekülstruktur im Kristall. mCPBA = meta-Chlorperbenzoesäure.

Oxidation of the Meroterpenoid (−)-Terreumol C from the Mushroom Tricholoma terreum: Discovery of Cytotoxic Analogues

“…(1aR,11aS,E)-7,10-Bis((tert-butyldimethylsilyl)oxy)-5-(hyd r o x y m e t h y l ) -8 -m e t h o x y -1 a -m e t h y l -1 a , 3 , 6 , 1 1 atetrahydrobenzo [4,5]cyclodeca [1,2-b]oxiren-11(2H)-one (7). To a suspension of SeO 2 (0.8 mg, 7.506 μmol) in DCM (0.5 mL) was added a solution of TBHP (5.5 M in decane, 10.2 μL, 56.298 μmol).…”

“…(1aR,11aS,E)-7,10-Dihydroxy-5-(hydroxymethyl)-8-methoxy-1a-methyl-1a,3,6,11a-tetrahydrobenzo [4,5]cyclodeca[1,2-b]oxiren-11(2H)-one (8). The bicycle 7 (6.1 mg, 11.447 μmol) was treated according to the general procedure for the desilylation of the TBS-protected hydroquinones.…”

“…Recently, we reported the total synthesis of terreumols A (1) and C (3), which provided terreumol C (3) in quantities above 100 mg, sufficient for further chemical studies. 5 Previously, only minor amounts were available (5.9 mg of 1 and 1.7 mg of 3 from 1 kg of dried fruiting body). 1 The key step of our synthesis was a ring-closing metathesis, which led to the formation of the 10membered ring with full control of the (Z)-configuration of the trisubstituted double bond between C6 and C7.…”

“…In this paper, we report on the behavior of (−)-terreumol C (3) under oxidative conditions. 5 We included the bis-(tert-butyldimethylsilyl) (TBS)-protected analogue 5, because the bulkiness of the TBS groups could alter the regioselectivity of certain reactions. Our goals were to gain insight into the reactivity of the positions of the southern rim and to assess the in vitro biological activities of new derivatives.…”

“…Encouragingly, epoxidation of (−)-terreumol C (3) to A (1) had proceeded with perfect diastereoselectivity. 5 Regarding the oxidative conditions to be investigated, we focused on the reactions of 3 and 5 with SeO 2 , Pd(II)/p-benzoquinone or tert-butyl hydroperoxide (TBHP), PhSeBr/LiOAc, N-bromosuccinimide (NBS) under ionic and radical conditions, dihydroxylation, Mn(III)/O 2 / TBHP, and ceric ammonium nitrate (CAN).…”