Purpurosamine synthesis

The L-sugar analogue 118 was prepared by C-5 inversion (sulfonate displacement) in an open chain intermediate en route to 117 (X=N3). A precursor for purpurosamine synthesis, 6-acetamido-3,4,6-trideoxy-D-glucal, was obtained in 63% e.e. by lipase-catalysed enantioselective JV-acetylation of the corresponding racemic acrolein-derived amine. Syntheses of various 4-deoxy-4-guanadino-analogues of. -acetylneuraminic acid and its 2-deoxy-2,3-unsaturated derivative, are covered in Chapter 16. 

The hetero-Diels-Alder reaction of activated butadienes with carbonyl compounds is a convenient method for the preparation of precursors of sugars. Up to three chiral centers are created simultaneously. The high-pressure [4 + 2]cycloaddition of l-methoxybuta-1,3-diene 32 to N-mono- and N,N-diprotected alaninals was investigated [42-45]. The Eu(fod)3-mediated reaction of 32 with alaninal 25 gave a mixture of four diastereoisomers, which was then subjected to acidic isomerization, leading to the thermodynamically more stable pair of adducts syn-33 and anti-34, with predominance of the latter isomer (Scheme 12). The N-monoprotected alaninals reacted with a moderate ryn-diastereoselectivity. This method was used in the synthesis of purpurosamines (see Sec. DI.C). 

A. Golfbiowski, U. Jacobsson, and J. Jurczak, High-pressure approach to the total synthesis of 6-epi-D-purpurosamine B, Tetrahedron 43 3063 (1987). 

T. Suami, Y. Honda, T. Kato, M. Masu, and K. Matsuzawa, Synthesis of methyl 2,6-di-A-acetyl-2,3,4,6,7-pentadeoxy-L-iyxo-heptopyranoside derivative of 6-epi-D-purpurosamine B, Bull. Chem. Soc. Jpn. 53 1372 (1980). 

Several years later Danishefsky introduced l-methoxy-3-trimethylsilyloxy-l,3-butadiene, a highly reactive diene, which upon reaction with (not activated) aldehydes catalyzed with mild Lewis acids [(Eu(fod)3] afforded cyclic a, -unsaturated ketones [19]. Another method involved reaction of l,4-di-alkoxy(acyloxy)-butadiene with an activated heterodienophile, which led to more functionalized derivatives (Schmidt) [20]. This methodology may be illustrated by the classical synthesis of the precursor of purpurosamine B (3) and higher sugar... 

Phosphonium salt 482, which can also be prepared from alcohol 437 by treatment with methyltriphenoxyphosphonium iodide followed by triphenylphosphine, has been used in a stereoselective synthesis of 6-ep/-D-purpurosamine B (494) (Scheme 69) [122]. A Wittig reaction of the ylide generated from 482 and Cbz-L-alaninal (488) affords the Z-olefin 489. lodocyclization gives the trans-cyclocaihamatQ 490 in quantitative yield. Removal of the iodo group, hydrolysis of the acetonide, and benzoylation fhmishes 491. 

The cleavage of A -benzoylepimino derivative 403 with acetic acid, resulting in the formation of 7-acetoxy derivative 406, was also reported in the later paper. In the synthesis of 6-epi-purpurosamine, a component of the antibiotic fort-imicin A, methyl 2-acetamido-6,7-(A-acetylepimino)-2,3,4,6,7-pentadeoxy-p-L-/yxo-heptopyranoside (408) reacted with acetic acid to give 6-acetoxy derivative 409 in 88% yield. °... 

Purpurosamine B (382), a seven-carbon atom sugar component of the antibiotic gentamicin C2, was synthesized from 6-acetyl-5,6-dihydio-2-methoxy-2H-pyran (333, R = Me). Oximation of the keto group, reduction of the oxime to the corresponding amine, and N-acetylation gave two stereoisomeric N-acet-amides. For further synthesis the erythro stereoisomer (380) was taken. Further steps involved the epoxldation of the double bond, isolation of the manno epoxide, and its reduction to methyl 6-acetamido-3,4,6,7-tetradeoxy-a-DL-araI)i>io-heptopyranoside (381). Oxidation of the 2-OH group, oximation of the ketone, and reduction of the oxime followed by acetylation gave methyl N,N -diacetyl-a-DL-purpurosaminide B, which was hydrolyzed to N,N -diacetyl-DL-purpuro-samine B (383). 

The two methyl pyranosides of 2-acetamido-2,3.4-trideoxy-D-er> f TO-hexose have been prepared as intermediates in the synthesis of purpurosamine C. The crucial intermediate in this synthesis was l,6-anhydro-3,4-dideoxy-2-0-tosyl- 8-D-t/zreo-hexopyranose (14) which underwent displacement of the sulphonyloxy... 

Istamycin A (4) and istamycin B (5) have been isolated from the culture broth of Streptomyces tenjimariensis, and sannamycin A (identical with istamycin A) and sannamycin B (6) from the culture broth of Streptomyces sannan-ensis- these are likewise 1,4-diamino-cyclitol ot-glycosides of 6-A -methyl-purpurosamine C. (The synthesis of this amino-sugar is mentioned in Chapter 8.) Derivatives of the amino-sugar and cyclitol constituents of fortimicin B have been prepared by benzyloxycarbonylation and alcoholysis of the antibiotic. ... 

The synthesis of 6-epz-purpurosamine B and other amino-sugar components of amino-glycoside antibiotics is referred to in Chapter 8. 

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