Total Synthesis of Sandresolide B and Amphilectolide

Abstract

The total synthesis of the diterpenoids sandresolide B and amphilectolide from a common furan building block is presented. Key steps include palladium-mediated carbonylation, lanthanide catalyzed ring closure, Myers alkylation, intramolecular Friedel-Crafts acylation, photooxygenation, and a Kornblum-DeLaMare rearrangement.

Marine natural products

“…762,763 and (AE)-tubastrindole B (Tubastraea sp. ), 764,765 butenolide (+)-hydroxyancepsenolide (Pterogorgia anceps), 766,767 and diterpenes sandresolide B, 768 amphilectolide 769 and (+)-ileabethoxazole 770 (Pseudopterogorgia elisabethae) 771,772 have been completed. Conversion of bipinnatin J (Pseudopterogorgia bipinnata) 773 to intricarene (Pseudopterogorgia kallos) 774 via a photochemical pathway has been demonstrated, 775 while a photochemical (E/Z) olen isomerisation was a critical step in the total synthesis of the natural product analog 17-deoxyprovidencin.…”

Rearrangements of organic peroxides and related processes

“…Amphilectolide was obtained through a photooxygenation of 325 in the presence of diisopropylethylamine (DIEA), followed by a one-pot reduction of the intermediate peroxide with sodium borohydride. Sandresolide B was prepared from 327 using tetraphenylporphyrin as a photosensitizer and DBU as a base in 51% yield over two steps ( Scheme 97 ) [ 377 ].…”

Furan Oxidation Reactions in the Total Synthesis of Natural Products

“…Further transformations of 33 produced cyclopentenes 34 and 35, which were converted into the target natural products; the conversion of 33 into all three natural lactones required six or seven steps (Scheme 9). 16 Baran and co-workers used the selective oxidation of the furan 40 synthesized from furfuryl alcohol (39) while working on the total synthesis of pallambins C (43) 3β-Methoxy-5α-androstan-17-one (45) was transformed into acetate 46, which was oxidized with singlet oxygen followed by treatment with NaBH 4 to afford the target compound (Scheme 11). 18…”

“…Finally, amphilectolide (96) was found to be formed from 95 in 11% yield only (Scheme 24). 39 Methylation of the related substrate 97 obtained from 4methyl-4-pentenoic acid and pseudoephedrine in four steps with MeMgBr followed by one-pot oxidation of the furan ring with 1 O 2 produced sandresolide B (98). However, Rose Bengal was found not to be a suitable sensitizer in order to produce the target product in reasonable yield.…”

“…Optimization of the reaction conditions showed that tetraphenylporphyrin (TPP) was the reagent of choice for the discussed reaction (Scheme 25). 39…”