Synthesis of the Fully Glycosylated Cyclohexenone Core of Lomaiviticin A

Abstract

We describe two four-step sequences for conversion of the inexpensive reagent ethyl sorbate to either O-allyl-N,N-dimethyl-D-pyrrolosamine or O-allyl-L-oleandrose, protected forms of the 2,6-dideoxy sugar residues found in the complex bacterial metabolite lomaiviticin A. We also report a gram-scale synthesis of the highly-oxygenated cyclohexenone ring of this metabolite, and show this may be coupled with the aforementioned donors to form the bis(glycoside) 6. The longest linear sequence to 6 is nine steps.

Methods for 2-Deoxyglycoside Synthesis

“…While many classes of donors failed to provide useful reactions with the heavily congested aglycone 72 , the investigators found that the use of glycosyl fluoride 71 provided the desired target 73 in moderate yield as a single isomer ( Scheme 23 ). 102 On the other hand, Zeng, Wan, and co-workers found that fluorides were not the optimal leaving group for coupling a ristosamine donor to C-4 of a galactose acceptor. 103 As a consequence, many other classes of dexoyglycosyl donors have been developed, often mirroring donors used in conventional glycosylation reactions.…”

Highly Efficient Acidic Etherification Using a Trichloroacetimidate for the Preparation of (4‐Chlorophenyl)(2‐pyridyl)methyl‐4‐piperidyl Ether, a Key Intermediate of Bepotastine

“…Although a catalytic amount (0.1 equiv) of various Lewis acids, such as TMSOTf, TfOH, HBF 4 , BF 3 ·OEt 2 , AgOTf, and Cu(OTf) 2 , was employed for the reactions of 4b with N ‐Boc‐4‐hydorxypiperidine ( 5 ) to obtain compound 3 based on the previous literature, the reaction yields were only ~5–30%. It has been reported that, in the case of the trichloroacetimdates containing an amino group, 2 equiv of BF 3 ·OEt 2 was used for etherification due to extra coordination of the Lewis acid with the amino nitrogen . Ether formation reactions of 4b with 5 were carried out in the presence of 0.1–1.0 equiv of Lewis acid, and the best results were obtained with 1.0 equiv of Lewis acids.…”

Synthesis of the N-(tert-butyloxycarbonyl)-O-triisopropylsilyl-d-pyrrolosamine glycal of lomaiviticins A and B via epimerization of l-Threonine

“…Recently, the synthesis of the N , N -dimethylpyrrolosamine carbohydrate found in both 1 and 2 has been addressed by our group5 as well as Herzon and coworkers 6. In this communication, we describe an alternative synthesis of the N , N -dimethylpyrrolosamine sugar that utilizes an interesting and useful epimerization reaction.…”