Total Synthesis of (±)-Garsubellin A

Abstract

The first total synthesis of garsubellin A, a neurotrophic compound with potent choline acetyltransferase-inducing activity, is described. Keys for success were (1) stereoselective intermolecular aldol reaction at the C-4 position with acetaldehyde, (2) stereoelective Claisen rearrangement to introduce an allyl group to the most sterically crowded position at C-6, (3) ring-closing metathesis to construct the B-ring, and (4) Wacker-type oxidative C-ring formation. This synthetic route can be extended to an asymmetric synthesis of garsubellin A using the Koga catalytic enantioselective alkylation, which produced enantioenriched alpha-prenyl cyclohexenone with excellent enantioselectivity (95% ee).

A New Fluorous Methoxymethyl (FMOM) Protecting Group for Alcohols

“…We next investigated deprotection of 4a under Brønsted and Lewis acidic conditions. Treatment of 4a with excess camphor sulfonic acid [15] (CSA, 10 equiv) in 2/1 THF/ MeOH for 11 h removed the F MOM group and returned geraniol in 79% yield after rapid chromatography. On the other hand, cleavage of 3a by ZnBr 2 [16] (3 equiv) and bu-tanethiol (2 equiv) in dichloromethane at r.t. provided geraniol in only 13% yield.…”

New Synthetic Methods for Hypericum Natural Products

“…21 The Shibasaki synthesis began with commercially available 3-ethoxycyclohex-2-enone, which underwent prenylation, methylation, and acid hydrolysis of the vinyl ether to yield an enone (Scheme 3). Conjugate addition of an methyl cuprate and in situ trapping of the resulting magnesium enolate by isobutyraldehyde gave the anti-aldol product, which was protected by TIPS to give 18.…”

Synthetic Studies Towards Bridgehead Diprenyl‐Substituted Bicyclo[3.3.1]nonane‐2,9‐diones as Models for Polyprenylated Acylphloroglucinol Construction

“…Concentration and purification by silica gel chromatography (dichloromethane) provided the enol lactone 19 (64.7 mg, 73 %) as a colorless oil. 3 solution in dry THF (0.15 mL, 150 µL) was slowly added to a solution of lactone 19 (38.1 mg, 0.12 mmol) in dry THF (120 µL) at -78°C. The mixture was stirred for 30 min at -78°C, warmed up to room temperature for 1 h, quenched by the addition of cold brine (2 mL), and filtered through Celite.…”

“…[2] The first total syntheses of a compound of this class, garsubellin A (type A PPAP), have been reported recently. [3] Our interest in this field arose from the observation [4] that xanthochymol (1) (Figure 2) was active in a tubulin disassembly inhibition test and from the recent isolation of the analogues oblongifolins A-D. [5] We also undertook syn-mation of a compound with gem-dimethyl substituents adjacent to the bridgehead position, but the construction of a suitably substituted enol lactone, with a view to polyprenylated acylphloroglucinol elaboration, could not be achieved.…”