Regioselective Diversification of a Cardiac Glycoside, Lanatoside C, by Organocatalysis

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The organocatalytic site-selective monoacylation of avermectin B 2a , an insecticidal and anti-parasitic drug, was accomplished. Although an acetylation of avermectin B 2a using a 4-dimethylaminopyridine (DMAP) as a catalyst gave poor site-selectivity, use of our organocatalyst increased site-selectivity of the acylation at the C-5-OH as well as the yield of monoacetate. This catalyst was also effective in other acylations. Interestingly, trihaloacetylation under same conditions gave poor site-selectivity. However, the use of an enantiomer of our organocatalyst provided the C-4″-O-trihaloacetyl avermectin B 2a with excellent siteselectivity. These results indicate that the site-selective acylation of avermectin B 2a can be controlled by the combination of a suitable organocatalyst and an acid anhydride.

Section: Resultsmentioning

confidence: 99%

Section: This Article Is Dedicated To Professor Satoshi ōMura In Celementioning

confidence: 99%

Organocatalytic Site-Selective Acylation of Avermectin B2a, a Unique Endectocidal Drug

Yamada

Suzuki

Hirose

et al. 2016

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“…Under these backgrounds, we have developed a method for a non-enzymatic site-selective acylation of polyol compounds such as natural glycosides catalyzed by 4-dialkylaminopyridine-type nucleophilic organocatalyst 6 and the derivatives [5][6][7][8][9][10] ( Fig. 1).…”

Section: )mentioning

confidence: 99%

“…This siteselectivity seems independent from the intrinsic reactivity of 5 itself, because 4-dimethylaminopyridine (DMAP)-catalyzed acylation provided the corresponding 3⁗-O-acylate in 97% site-selectivity. 8) Thus, introduction of the acyl group at the C(4⁗)-OH was performed by catalyst-controlled manner and that at C(3⁗)-OH was done by substrate-controlled manner. In the course of our continuous efforts for site-selective diversification of polyol natural products, we found that catalyst 6 promoted highly site-selective acylation of 10-deacetylbaccatin III (1) at the C(10)-OH, which is a natural terpenoid available in relatively abundant amount and used as a key intermediate for clinically widely used antitumor agents, taxol (4) and taxotere (3) (Fig.…”

Section: )mentioning

confidence: 99%

Organocatalytic Site-Selective Acylation of 10-Deacetylbaccatin III

Yanagi

Ninomiya

Ueda

et al. 2016

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Organocatalytic site-selective diversification of 10-deacetylbaccatin III, a key natural product for the semisynthesis of taxol, has been achieved. Various acyl groups were selectively introduced into the C(10)-OH of 10-deacetylbaccatin III. The C(10)-OH selective acylation was also applied to acylative site-selective dimerization of 10-deacetylbaccatin III to provide the structurally defined dimer.

“…2). For example, site-selective acylation of lanatoside C (5) took place at the C(4⁗)-OH in 86% site-selectivity among eight hydroxy groups in the different micro environments in the presence of catalyst 1 14) (Fig. 2).…”

Section: )mentioning

confidence: 99%

A Concise Access to C2-Symmetric Chiral 4-Pyrrolidinopyridine Catalysts with Dual Functional Side Chains

Mishiro

Takeuchi

Furuta

et al. 2016

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A practical method was developed for the preparation of a diastereomeric library of C 2 -symmetric chiral 4-pyrrolidinopyridine catalysts with dual amide side chains. Use of a racemic precursor is the key to the concise production of catalysts with diverse stereochemisty.Key words organocatalyst; C 2 -symmetry; pyrrolidinopyridine; catalyst library; racemic precursor Various chiral 4-dimethylaminopyridine (DMAP) and 4-pyrrolidinopyridine (PPY) derivatives have been developed and extensively employed in asymmetric acyl transfer and the related reactions.1-6) Especially, C 2 -symmetric-2,5-disubstituted PPY is a privileged structure for site-and chemoselective molecular transformation. For example, catalyst 1 was found to be effective for site-selective acylation of glycopyranoside derivatives, 7-11) chemoselective monoacylation of linear diols, 12) and site-selective acylation of a cardiac glycosides, digitoxin 13) and lanatoside C (5) 14) (Fig. 1). Highly geometryselective acylation of tetra-substituted α,α′-alkenediols has been also achieved by employing catalyst 2a.15) Catalyst 2b was found to be effective for chemoselective acylation of sterically hindered secondary alcohols in the presence of otherwise more reactive primary alcohols.16) Asymmetric desymmetrization of meso-diols has been performed by catalyst 3 17) (Fig. 1). All of these C 2 -symmetric PPY catalysts have been prepared from versatile precursor 4. 7)For the above-mentioned site-and chemoselective molecular transformations, precise molecular recognition process between the catalysts and the substrates seems to be involved. 18,19) The amide side chains at C(2) and C(5) of the pyrrolidine ring are assumed to be responsible for the molecular recognition process. Therefore, preparation of all four possible isomers of C 2 -symmetric PPY catalysts with dual chiral amide side chains at C(2) and C(5) such as 1, 1a, ent-1, and ent-1a seemed to be meaningful for optimizing the conditions for the targeted site-selective molecular transformation (Fig. 2). For example, site-selective acylation of lanatoside C (5) took place at the C(4⁗)-OH in 86% site-selectivity among eight hydroxy groups in the different micro environments in the presence of catalyst 1 14) (Fig. 2). On the other hand, the diastereomeric and enantiomeric catalysts 1a, ent-1, and ent-1a gave the C(4⁗)-, C(3⁗)-, and C(3⁗)-O-acylates as the major acylate in 73, 62, and 80% site-selectively, respectively. Accordingly, site-selectivity of the acylation was critically affected by the nature and stereochemistry of the amide side chains at C(2) and C(5) of the pyrrolidine ring of the PPY catalysts.These four diastereomeric catalysts have been prepared from versatile precursor 4 and its enantiomer. We have reported a method for the preparation of 4 starting from L-pyroglutamic acid (6) via tedious five-step sequence in 16% overall yield 7) (Fig. 3A). Large-scale preparation of 4 has been often problematic because of poor reproducibility of the transformation from 7 to 8 with catalytic amount of CuI....