Total Synthesis of Trioxacarcin DC‐45‐A2

Abstract

An enantioselective total synthesis of trioxacarcin DC-45-A2 (1) featuring a novel Lewis acid-induced cascade rearrangement of epoxyketone 6 to forge the polyoxygenated 2,7-dioxabicyclo[2.2.1]heptane core of the molecule is described.

Total Synthesis of (±)‐Phyllantidine: Development and Mechanistic Evaluation of a Ring Expansion for Installation of Embedded Nitrogen‐Oxygen Bonds

“…Efforts toward 1 began as shown in Scheme 3w ith preparation of known mono TBS-protected diol 19 [19] from 1,4-cyclohexadiene (20). Upjohn dihydroxylation of 20 [20] and subsequent protection with tert-butyldimethylsilyl chloride (TBSCl) proved to be the most effective sequence to deliver multi-gram quantities of 19.O xidation of alcohol 19 with Dess-Martin periodinane (DMP) gave the desired a-silyloxy ketone 22 in 87 %yield, without any observable isomerization of the olefin.…”

“…Efforts toward 1 began as shown in Scheme 3w ith preparation of known mono TBS-protected diol 19 [19] from 1,4-cyclohexadiene (20). Upjohn dihydroxylation of 20 [20] and subsequent protection with tert-butyldimethylsilyl chloride (TBSCl) proved to be the most effective sequence to deliver multi-gram quantities of 19.O xidation of alcohol 19 with Dess-Martin periodinane (DMP) gave the desired a-silyloxy ketone 22 in 87 %yield, without any observable isomerization of the olefin. Subsequent aldol addition of the lithium enolate, derived from cyclopentanone,p roceeded as expected to the least hindered diastereotopic face of ketone 22 and, to our delight, with complete selectivity for the illustrated relative stereochemistry between the two newly formed stereogenic centers,t hus producing 18 as the only isolable product.…”

“…By lowering the temperature to À80 8 8Ci nT HF solvent, albeit with longer reaction times (50 h), (Table 1Entry 13) 49 could be obtained exclusively! Thelast factor evaluated was whether the metal counterion was important in obtaining this high degree of regioselectivity (Table 1, Entries [19][20][21]. Ther ate of reaction was found to follow the expected trend for metal alkoxides (KOMe > NaOMe > LiOMe), [35] and, since the basicity of LiOMe is moderated in ethereal solvents due to aggregation effects, [35,36] it results in less carbonate cleavage products (50 and 51).…”

ChemInform Abstract: Practical Synthesis of p‐ and o‐Amino‐ and Methoxyphenolic Anthraquinones.

“…Examples of such compounds abound and include the biologically active enediynes [1,2] (e.g.u ncialamycin, Figure 1a), [3][4][5][6] tetracycline antibiotics [7] (e.g.v iridicatumtoxin B), [8][9][10] and trioxacarcins [11][12][13][14] (e.g. Examples of such compounds abound and include the biologically active enediynes [1,2] (e.g.u ncialamycin, Figure 1a), [3][4][5][6] tetracycline antibiotics [7] (e.g.v iridicatumtoxin B), [8][9][10] and trioxacarcins [11][12][13][14] (e.g.…”

“…Aminoand methoxy-anthraquinones and related systems are common structural motifs of natural and designed molecules of biological, medical and industrial importance. Examples of such compounds abound and include the biologically active enediynes [1,2] (e.g.u ncialamycin, Figure 1a), [3][4][5][6] tetracycline antibiotics [7] (e.g.v iridicatumtoxin B), [8][9][10] and trioxacarcins [11][12][13][14] (e.g. DC-45-A2) classes of natural products as well as the brightly colorful compounds alizarin and carminic acid (crimson, cochineal).…”