Total Synthesis of (±)-Phomoidride†D.

Described herein is a synthetic strategy for the total synthesis of (±)-phomoidride D. This highly efficient and stereoselective approach provides rapid assembly of the carbocyclic core by way of a tandem phenolic oxidation/intramolecular Diels-Alder cycloaddition. A subsequent SmI2 -mediated cyclization cascade delivers an isotwistane intermediate poised for a Wharton fragmentation that unveils the requisite bicyclo[4.3.1]decene skeleton and sets the stage for synthesis completion.

Cascade- and orthoamide-type Overman rearrangements of allylic vicinal diols.

This article describes the details of two new types of Overman rearrangement from allylic vicinal diols. Starting from identical diols, both bis(imidate)s and cyclic orthoamides were selectively synthesized by simply changing the reaction conditions. Whilst exposure of the bis(imidate)s to thermal conditions initiated the double Overman rearrangement to introduce two identical nitrogen groups in a single operation (the cascade-type Overman rearrangement), the reaction of cyclic orthoamides resulted in a single rearrangement (the orthoamide-type Overman rearrangement). The newly generated allylic alcohols from the orthoamide-type reaction can potentially undergo a variety of further transformations. For instance, we demonstrated an Overman/Claisen sequence in one pot. The most conspicuous feature of this method is that it offers precise control over the number of Overman rearrangements from the same allylic vicinal diols. This method also excludes the tedious protecting-group manipulations of the homoallylic alcohols, which are necessary in conventional Overman rearrangements. All of the performed rearrangements proceeded in a completely diastereoselective fashion through a chair-like transition state.

Toward the synthesis of phomoidride D.

An efficient and highly stereoselective approach toward the phomoidride family of natural products is described. The carbocyclic core structure was assembled using a tandem phenolic oxidation/Diels-Alder cycloaddition and a tandem 5-exo-trig/5-exo-trig radical cyclization to deliver an isotwistane intermediate that, upon a late-stage xanthate-initiated Grob fragmentation, furnishes the requisite bicyclo[4.3.1]decene.

Wharton-fragmentation-based approach to the carbocyclic core of the phomoidrides.

The carbocyclic core of the phomoidrides has been synthesized efficiently and in high yield. Key steps include a phenolic oxidation/intramolecular Diels-Alder sequence, tandem radical cyclization, and a late-stage Wharton fragmentation of a densely functionalized isotwistane skeleton.

Total synthesis of broussonetine F: the orthoamide Overman rearrangement of an allylic diol.

A first total synthesis of broussonetine F from diethyl L-tartrate was achieved. The cornerstone of our synthesis was an orthoamide Overman rearrangement, which provided an allylic amino alcohol with complete diastereoselectivity.

Total synthesis of (-)-agelastatin A: the application of a sequential sigmatropic rearrangement.

An enantioselective total synthesis of (-)-agelastatin A from (-)-2,3-O-isopropylidene-d-threitol is described. The sequential Overman/Mislow-Evans rearrangement of the allylic bistrichloroimidate is the key step, which efficiently installed a diaminohydroxy group.

Detection of mucosal human papilloma virus DNA in bowenoid papulosis, Bowen's disease and squamous cell carcinoma of the skin.

Human papilloma virus (HPV) is known to be an etiologic agent for benign warts of the skin. Recently, HPV have been detected in malignant skin and mucosal diseases suggesting that HPV infection can induce malignant skin tumors. In the present study, we examined the presence of mucosal HPV DNA in normal tissue, Bowen's disease (BD), Bowenoid papulosis (BP) and squamous cell carcinoma (SCC) of the skin. We detected the HPV DNA with polymerase chain reactions, and identified the type by DNA sequencing. In the results, we detected HPV DNA in none of the 17 normal controls, two of the three BP (66.7%), one of the 21 BD (4.8%), and six of the 26 SCC of the skin samples (23.0%). The occurrence rates of HPV in BP and SCC were significantly elevated compared to that of normal controls (P < 0.01 and P < 0.01, respectively). In addition, the occurrence rate of HPV in BP was significantly elevated compared to that of BD (P < 0.05). The reproducibility was confirmed with a polymerase chain reaction (PCR) with another primer pair. Of the two cases of BP with positive HPV DNA, one case showed HPV 31 and the other case HPV 16. The case of BD with positive HPV DNA showed HPV 31. Of the six cases of SCC with positive HPV DNA, one case showed HPV 16, another case HPV 34, and the other four cases HPV 31. These results showed that mucosal HPV, including HPV 31 and 16, could be detected in SSC of the skin. Mucosal HPV, not only the epidermodysplasia verruciformis type, appear to induce malignant skin tumors.

Novel mutation in ATP2C1 gene in a Japanese patient with Hailey-Hailey disease.

Hailey-Hailey disease (HHD) is an autosomal dominant disorder with recurrent eruption of vesicles and bullae involving predominantly the neck, groin and axillary regions. Histopathology shows suprabasal cleavage in epidermal cells. Recent studies have revealed that HHD is caused by mutations in the ATP2C1 gene encoding a novel Ca(2+) pump. We analyzed mutations of the ATP2C1 gene in 2 Japanese patients with HHD. The diagnosis of HHD was made based on the characteristic clinical features and histopathological evidence. All 27 exons and flanking intron boundaries were amplified by polymerase chain reaction and products analyzed by sequencing. As a result, we identified a novel missense mutation (A1087G) in exon 13 of the ATP2C1 gene in a patient. This mutation led the amino acid change from Thrto Ala in the phosphorylation protein domain. Another patient showed no mutation of the gene. These results demonstrate that a spectrum of ATP2C1 gene mutations is present in Japanese HHD patients.

Squamous cell carcinoma of the penis in a man with a human papilloma virus 31 infection.

We report a 51-year-old man with squamous cell carcinoma (SCC) on his penis. He was surgically treated for his phimosis when he was 20 years old. He presented with an indurated nodule on the tip of his penis. The tumor was treated with partial penectomy and standard inguinal lymphadenectomy. Histological examination revealed that the tumor was a well-differentiated type of SCC. A polymerase chain reaction was performed to detect human papilloma virus (HPV) DNA. The result revealed the presence of HPV in the SCC. The results of sequencing analysis showed that the DNA was HPV 31.