Studies on the Synthesis of Acanthodoral and Nanaimoal:  Evaluation of Cationic Cyclization Routes

Abstract

Intramolecular Lewis acid-promoted reactions of α,β-unsaturated ketone 6 and aldehydes 7 and 8 were examined as potential routes to acanthodoral (1), a structurally interesting natural product. Ketone 6 afforded ene product 22 exclusively, and both 7 and 8 gave mixtures of bicyclic aldehydes 3 and 26 and tricyclic aldehyde 25. The latter most likely results from 7 by intramolecular cyclization of the alkene onto the Lewis acid-activated carbonyl moiety affording carbocation 31 followed by a 1,2-hydride shift and ring closure. Starting from 8, tricyclic aldehyde 25 apparently forms by cyclization to cation 35 and ring closure to cyclobutane 36, followed by ring opening to 31, the same cation as formed in reactions of 7. Nanaimoal (3) results from loss of H+ from 31, and bicyclic aldehyde 26 may be formed in a similar manner or by a concerted ene reaction. The configuration of 25 establishes that the stereochemistry of the initial cyclization to 31 precludes the possible use of this strategy for the synthesis of acanthodoral. However, acid-promoted cyclization of allylic alcohol 23 efficiently gives diene 29 which undergoes selective hydroboration/oxidation to afford nanaimoal.

Benwamycins A–G, Trialkyl-Substituted Benzene Derivatives from a Soil-Derived Streptomyces

“…This proposal was confirmed by correlations from H 3 -15 to C-5, C-6, and C-7 (Figure ). In order to confirm the absolute configuration of 2 , the known compound 10 was reduced by NaBH 4 , yielding 2 and its C-13 epimer 2a (Scheme S1, Figure S1, and Table S4). The 10 S -configuration of 2 was identical to that of 1 and 10 , because of similar Cotton effects in the CD spectrum (Figure ).…”

“…NaBH 4 Reduction of 10. According to the previously described procedure, 17 sodium borohydride (73 mg, 1.96 mmol) was added to a solution of 10 (60 mg, 0.22 mmol) in methanol (12 mL). After 30 min at room temperature, the mixture was treated with saturated aqueous ammonium chloride and extracted with CH 2 Cl 2 .…”

Zeolite NaY-Promoted Cyclization of Farnesal: A Short Route to Nanaimoal

“…The major product (50% relative yield; 30% isolated yield after column chromatography) was the bicyclic aldehyde 1a obtained as a 92/8 mixture of diastereomers (GC−MS), with the major one shown in Scheme . Aldehyde 1a is a double-bond isomer of the naturally occurring nanaimoal ( 2 ), a sesquiterpene with a unique carbon skeleton, isolated from the nudibranch Acanthodoris nanaimoensis .…”

Total Synthesis of (+)-Acanthodoral by the Use of a Pd-Catalyzed Metal-ene Reaction and a Nonreductive 5-exo-Acyl Radical Cyclization

“…In connection with our continued interest in the development of approaches toward the synthesis of strained natural products, we set out to investigate the total synthesis of acanthodoral ( 1 ). , Our initial attempts at directly constructing the bicyclo[3.1.1]heptane system by a tandem 6- endo- acyl radical/4- exo -alkyl radical cyclization sequence (see, e.g., structure X above) were not successful presumably due to its insurmountably severe strain energy (SE) . We, therefore, opted for an indirect approach that involves initial assembly of the substantially less strained bicyclo[3.2.1]octane system followed by a ring contraction to the desired bicyclo[3.1.1]heptane system.…”