Synthesis of the N-(tert-butyloxycarbonyl)-O-triisopropylsilyl-d-pyrrolosamine glycal of lomaiviticins A and B via epimerization of l-Threonine

Morris, William; Shair, Matthew D.

doi:10.1016/j.tetlet.2010.06.028

Cited by 18 publications

(9 citation statements)

References 23 publications

(6 reference statements)

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“…Under these conditions, the hydroxyfulvene is deprotonated to generate a cyclopentadienyl anion. Attack of this anion on the triflyl azide reagent provides the observed product (93). It is noteworthy that although the anionic charge of the conjugate base of 106 is delocalized over the entire cyclopentadiene ring, only diazotransfer to the desired position generates a stable product.…”

Section: Enantioselective Synthesis Of (à)-Kinamycin F (Herzon and Co...mentioning

confidence: 97%

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The diazofluorene antitumor antibiotics: Structural elucidation, biosynthetic, synthetic, and chemical biological studies

Herzon

Woo

2012

Nat. Prod. Rep.

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This review presents a comprehensive survey of all aspects of the kinamycins and lomaiviticins, potent antiproliferative antimicrobial metabolites isolated from various strains of Streptomyces and Salinispora. The kinamycins and lomaiviticins contain a diazotetrahydrobenzo[b]fluorene (diazofluorene) functional group, which is unique among known natural products. This review begins with an account of the studies leading to the final (correct) structure determination of the kinamycins, which were originally proposed to contain an N-cyano carbazole function. This is followed by a discussion of biosynthetic studies, which established the polyketide nature of the kinamycins. Descriptions of four completed syntheses of various kinamycins, synthetic studies toward the lomaiviticins, syntheses of the carbohydrates of the lomaiviticins, and syntheses of structurally-related metabolites, are then presented. A survey of chemical biological investigations, including in vitro reactivity studies, which indicate that the kinamycins and lomaiviticins may form reactive ortho-quinone methide or free radical intermediates in vivo, is presented. Finally, a selection of structurally-related metabolites are described.

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Section: Enantioselective Synthesis Of (à)-Kinamycin F (Herzon and Co...mentioning

confidence: 97%

“…Shair and co-workers have published two approaches to N,Ndimethyl-pyrrolosamine (223) 92,93 as well as a direct method for the synthesis of b-linked 2-deoxyglycosides by O-alkylation. Shair's first approach to 223 begins with the known glycal 225 (Scheme 43).…”

Section: Synthesis Of the Pyrrolosamine Residue And The Direct Format...mentioning

confidence: 99%

The diazofluorene antitumor antibiotics: Structural elucidation, biosynthetic, synthetic, and chemical biological studies

Herzon

Woo

2012

Nat. Prod. Rep.

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“…16 The same group reported two syntheses of the protected pyrrolosamine residue of the lomaiviticins. 16,17 Many groups have also conducted studies aimed at elucidating the origins of the cytotoxic effects of the kinamycins and lomaiviticins, 18 although a complete understanding of the fate of these metabolites in vivo has not yet been obtained.…”

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confidence: 99%

Enantioselective Syntheses of (-)-Kinamycin F and (-)-Lomaiviticin Aglycon

Herzon¹

2011

Synlett

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Synthetic studies of the diazofluorene antitumor antibiotics, the kinamycins and lomaiviticins, are described.The kinamycins 1-3 and lomaiviticins 5, 6 constitute a unique family of bacterial metabolites with unusual molecular architectures and powerful anticancer and antimicrobial activities (Figure 1). 1 The kinamycins were first isolated in the early 1970s by Omura and co-workers. 2 Contributions from several research groups, 3 over a period of nearly 25 years, established their molecular structures and revealed the presence of a diazotetrahydrobenzo[b]fluorene (diazofluorene) functional group, which had not been previously identified among natural products. Many different kinamycins are now known, and these are distinguished primarily by the acylation pattern about the oxygenated D-ring. Kinamycins A (1), 2 C (2), 2 and F (3) 4 are representative.In 2001, the C 2 -symmetric metabolites lomaiviticins A and B (5 and 6, respectively) were isolated in a collaborative effort by researchers at Wyeth and the University of Utah. 5 The lomaiviticins share the signature diazofluorene of the kinamycins, but several structural differences exist between the two classes of metabolites. Most notably, the two halves of the lomaiviticins are united by a single carbon-carbon bond (red in 5 and 6). Within lomaiviticin B (6), the tertiary (C-3/C-3′) hydroxyl groups have undergone 1,2-addition to the adjacent ketone functions, to form a rigid bis(tetrahydrofuranol) structure. Additional significant differences include the presence of dihydroxynaphthoquinone residues in the lomaiviticins (as opposed to a juglone residue in the kinamycins) and 2-4 2,6-dideoxyglycosides, a-oleandrose, and b-N,N-dimethylpyrrolosamine, about the periphery of the lomaiviticins.In 2008 our research group embarked on a journey to synthesize the kinamycins and lomaiviticins. Our studies have yielded a general route to the diazofluorene substructure, as well as syntheses of kinamycin F (3), 6 lomaiviticin aglycon (4), 7 and the carbohydrate residues 8 of the lomaiviticins. Prior to, and contemporaneous with, our own studies, several other groups have also advanced this area of research. The Porco, 9 Nicolaou, 10 and Ishikawa 11 research groups developed syntheses of several kinamycins, which preceded our work in this area. These investigations provided the first insights into the stability and reactivity of the diazofluorene functional group in multistep synthetic settings.

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“…Recently, Morris and Shair demonstrated the utility of the Rh-catalyzed cycloisomerization in the formation of an intermediate glycal for the synthesis of lomaiviticin A and B. [51] In our synthesis of laulimalide, we were interested in exploring the scope of the reaction by employing a challenging diyne substrate 13 . The success of this cycloisomerization step would rely on the reversibility of the Rh-vinylidene formation and the kinetically more facile production of the six-membered cyclic glycal product over a seven-membered ring.…”

Section: Rh(i) Cycloisomerization For the Synthesis Of The Southern Fmentioning

confidence: 99%

Total Synthesis of Laulimalide: Synthesis of the Northern and Southern Fragments

Trost

Seganish

Chung

et al. 2012

Chemistry A European J

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The first stage of the development of a synthetic route for the total synthesis of laulimalide (1) is described. Our retrosynthetic analysis envisioned a novel macrocyclization route to the natural product using a Ru-catalyzed alkene-alkyne coupling. This would be preceded by an esterification of the C19 hydroxyl group, joining together two equally sized synthons, the northern fragment 7 and the southern fragment 8. Our first generation approach to the northern fragment entailed a key sequential Ru-Pd coupling sequence to assemble the dihydropyran. The key reactions proceeded smoothly, however, the inability to effect a key olefin migration led to the development of an alternative route based on an asymmetric dinuclear Zn-catalyzed aldol reaction of a hydroxyl acylpyrrole. This key reaction led to the desired diol adduct 66 with excellent syn:anti selectivity (10:1), and allowed for the successful completion of the northern fragment 7. The key step for the synthesis of the southern fragment was a chemoselective Rh-catalyzed cycloisomerization reaction to form the dihydropyran ring from a diyne precursor. This reaction proved to be selective for the formation of a six-membered ring, over a seven. The use of an electron-deficient bidentate phosphine allowed for the reaction to proceed with a reduced catalyst loading.

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Synthesis of the N-(tert-butyloxycarbonyl)-O-triisopropylsilyl-d-pyrrolosamine glycal of lomaiviticins A and B via epimerization of l-Threonine

Cited by 18 publications

References 23 publications

The diazofluorene antitumor antibiotics: Structural elucidation, biosynthetic, synthetic, and chemical biological studies

The diazofluorene antitumor antibiotics: Structural elucidation, biosynthetic, synthetic, and chemical biological studies

Enantioselective Syntheses of (-)-Kinamycin F and (-)-Lomaiviticin Aglycon

Total Synthesis of Laulimalide: Synthesis of the Northern and Southern Fragments

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