Synthesis of regioisomeric analogues of crisamicin A

Abstract

The synthesis of bis-furonaphthopyrans 12a and 12b, regioisomeric analogues of the dimeric pyranonaphthoquinone antibiotic crisamicin A 1 is described. The key intermediate 16 was prepared via a one-pot in situ Suzuki-Miyaura homocoupling of naphthyl triflate 23 using bis(pinacolato)diboron. Oxidation of binaphthyl 16 to bis-naphthoquinone 14 was then effected with silver(II) oxide and nitric acid. Efficient double furofuran annulation of bis-naphthoquinone 14 with 2-trimethylsilyloxyfuran 8 afforded bis-furonaphthofuran adducts 13a and 13b as an inseparable 1:1 mixture of diastereomers. Oxidative rearrangement of this mixture of bis-furonaphthofuran adducts 13a and 13b using silver(II) oxide and nitric acid afforded unstable bis-furonaphthopyrans 12a and 12b also as a 1:1 mixture of diastereomers. Addition of 2-trimethylsilyloxyfuran 8 to naphthoquinone 25 afforded adduct 26 that underwent oxidative rearrangement to furonaphthopyran 27, however attempts to effect Suzuki-Miyaura homocoupling of triflates 26 and 27 to their respective dimers 13 and 12, was unsuccessful.

Dimeric Pyranonaphthoquinones: Isolation, Bioactivity, and Synthetic Approaches

“…[106] Here the acetyl function was installed at an early stage because the late-stage Fries rearrangement had not worked earlier (Scheme 7). [106] Here the acetyl function was installed at an early stage because the late-stage Fries rearrangement had not worked earlier (Scheme 7).…”

“…Brimble and co-workers achieved the synthesis of regioisomeric analogues of crisamicin A from naphthyl triflate 94 (Scheme 8). [106] Here the acetyl function was installed at an early stage because the late-stage Fries rearrangement had not worked earlier (Scheme 7). Suzuki-Miyaura homocoupling of 102 (synthesized from 94, Scheme 8) in the presence of 95 provided a bis-acetylnaphthalene, which upon effective oxidation with freshly prepared silver(II) oxide and 6 M HNO 3 provided the unstable bis-acetylnaphthoquinone 103.…”

Pyranonaphthoquinones—isolation, biological activity and synthesis

“…Finally, CAN-mediated oxidative rearrangement effected smooth conversion to pyranonaphthoquinones 67a-b, regioisomeric analogues of antibiotic crisamicin A 18 (Scheme 9). 28…”

Toward an Asymmetric Synthesis of the Dimeric Pyranonaphthoquinone Antibiotic Crisamicin A

“…The pyranonaphthoquinones are a large group of natural products that have attracted the attention of our research group . While we have successfully synthesized the simpler monomeric structures of this family of natural products, of significant interest to us are the more complex dimeric pyranonaphthoquinones such as crisamicin A 1 , actinorhodin 2 and cardinalin 3 3 (Figure ). These natural products are characterized by a C8–C8′ biaryl linkage with various substitution around the pyranonaphthoquinone ring system.…”

“…Our earlier synthetic work toward crisamicin A 1 focused on the use of a Suzuki coupling to construct the dimeric framework followed by a double furonaphthofuran rearrangement to form the pyranonaphthoquinone; however, this strategy only afforded regioisomers of crisamicin A 1 . ,, A later attempt probed the use of a double Hauser–Kraus (HK) annulation using a bis-cyanophthalide to afford a dimeric naphthalene intermediate that was not able to be further elaborated to crisamicin A 1 . However, this HK annulation approach was successfully used to construct the core of the related dimeric pyranonaphthoquinones, the cardinalins .…”