Tackling the Challenges in the Total Synthesis of Landomycin A

Abstract

The twists and turns toward the total synthesis of landomycin A, a prominent angucycline hexasaccharide antibiotic, in particular those toward the stereoselective construction of the di- and trideoxyglycosidic linkages, are described.

Total Synthesis of Jadomycins B, S, T, and ILEVS1080

“…[9] Previously, we have carefully studied the glycosylation of a similar angucycline phenol in landomycins and solved the problem by S N 2 substitution of a glycosyl a-iodide with the angucycline phenolate. [13] Thus, we attempted the glycosylation of 7 with 3,4-di-O-acetyl-l-digitoxosyl iodide, which was prepared in situ from the corresponding acetate 8 (TMSI, CH 2 Cl 2 , 0 8C), [12,14,15] in the presence of KHMDS and [18]C-6 in THF. The reaction led to a complex mixture of products (Table 2, entry 1); detection of glycal derivatives in the mixture indicated the vulnerability of the digitoxosyl iodide to decomposition under the reaction conditions.…”

“…In fact, the stability of the glycosyl iodide (which contains an electronwithdrawing substituent at C6) has been found to be crucial to the successful glycosylation in the landomycin synthesis. [13] We therefore attempted the glycosylation with the more stable glycosyl bromide (derived in situ from acetate 8 with TMSBr). [12] Indeed, the desired glycoside 11 was iso-A C H T U N G T R E N N U N G lated, albeit in only a moderate yield of 25 % with no a/b selectivity (Table 2, entry 2).…”

Total synthesis of landomycins Q and R and related core structures for exploration of the cytotoxicity and antibacterial properties

“…1b). 22 To tackle these challenges, new synthetic routes were designed, which was based on the modications of literature protocols. [19][20][21] To access anhydrolandomycinone core (1) and its B-ring unsaturated analogue (2), the D-ring and A-ring building blocks 5 and 6 were prepared from available hydroquinone 7 and dimethylanisole 8, respectively.…”

Applications of Mitsunobu Reaction in total synthesis of natural products

“…It displays Significant and strong activity against certain cancer cell lines . (The twists and turns toward the total synthesis of 332 as unique antibiotic reported by Yu and co‐workers in 2013 . The glycosylation of phenol 335 commenced by coupling of thiomannoside acceptor 333 and 2,3‐O‐thionocarbonyl‐1‐thio‐a‐mannoside 334 in several steps .…”