Enantiospecific Formal Total Synthesis of Iriomoteolide 3a

Abstract

A formal total synthesis of the marine macrolide iriomoteolide 3a is described. Salient features of the synthesis include the elaboration of a β-keto phosphonate derived from D-(-)-tartaric acid and the extension of a chiral butyrolactone derived from L-glutamic acid. Ring-closing metathesis is employed to construct the macrolactone core of the natural product.

Total Synthesis of Callyspongiolide: An Anticancer Marine Natural Product

“…According to the retrosynthetic plan, our synthesis commenced from known compound 14 , which was prepared on a multigram scale via conjugate addition of allyltrimethylsilane to α,β-unsaturated N -acyloxazolidinone 13 . 10 The removal of chiral auxiliary from 14 with LiBH 4 produced an alcohol, which on protection with TBDPSCl in the presence of Et 3 N in CH 2 Cl 2 furnished compound 12 in 89% over two steps. To fix the C7-hydroxy center of the molecule, the olefinic moiety of compound 12 was subjected to epoxidation with m -CPBA to furnish a diastereomeric mixture of terminal epoxide, which on hydrolytic kinetic resolution with ( R,R )- 12a salen provided diastereomerically pure terminal epoxide 15 (de > 92%, 40%) and diol compound 16 (de > 90%, 44%).…”

The Synthesis and Bioactivity of the Marine Macrolide Callyspongiolide

“…The total synthesis by S. Ghosh et al. began with the known [50, 51] asymmetric addition of allyltrimethylsilane to N ‐acyloxazolidinone 124 . The amide was reduced to an alcohol, which was protected as a tert ‐butyldiphenylsilyl ether to give alkene 125 .…”

Recent Advances in Total Synthesis via Metathesis Reactions

“…For this reason, in this section, we would like to highlight representative examples reported in the last few years in which the RCM reaction was the key step. As a first series of examples in this category, it is worth mentioning the polyketide-type compounds ripostatin B (28) 35 and A (29), 36 FD-895 (30), 37 cruentaren A (31), 38 pikromycin (32), 39 zampanolide (33), 40 amphidinolide G (34), 41 palmerolide A (35), 42 ecklonialactone B (36), 43 gambieric acid A (37), 44 nominal gobienine A (38), 45 trienomycin A (39) and F (40), 46 13-demethyllyngbyasolide B (41), 47 incednam (42), 48 sekothrixide (43), 49 aspicillin (44), 50 macrolide fragment of FD-891 (45), 51 carolacton (46) 52 ( Figure 2), cytospolide P (47), 53 pectenotoxin (48), 54 Sch725674 (49), 55 aspergillide B (revised structure, 50), 56 iriometolide 3a (51), 57 paecilomycin B (52), 58 fidaxomicin (53), 59 exiguolide (54), 60 neopeltolide (55), 61 methynolide (56), 62 and iriomoteolide-2a (57) 63 (Figure 3). In addition, the group of alkaloids and cyclodepsipeptides are illustrated with the examples of manzamine A (58), 64 isoschizogamine (59), 65 vertine (60), 66 haliclamide (61), 67 5-epi-torrubiellutin (62), 68 petrosin (63), 69 the YM-254890 analogue 64, 70 nannocystin A (65) and A0 (66), 71 nakadomarin A (67), 72…”

“…A stunning example of the power of the RCM reaction can be found in the construction of strained ring systems via a transannular process as applied in the recent synthesis of the cembranolides sarcophytonolide H (92) and isosarco- Iriomoteolide-2a (57) (Fuwa, 2018) [63] O O (Mohapatra, 2014) [56] RCM O C 5 H 11 OH OH OH O Sch725674 (49) (Prasad, 2014) [55a] (Kumar, 2016) [55b] RCM (82%) (36%) [55a] (70%) [55b] (Prasad, 2014) [57] ( (Ohba, 2015) [58] (81%)…”