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Podophyllotoxin and epi-podophyllotoxin derivatives (1/2) with an unsaturated side chain at C-5a were obtained by C-alkylation of protected derivatives of 1. The azide 3a afforded 4 in quantitative yield at 80°C. With pyridine/acetyl chloride, the latter yielded the rigid epi-podophyllotoxin derivative 7, whose structure was established by crystal structure analysis. All reported podophyllotoxin derivatives are less cytotoxic than podophyllotoxin (1a) itself.

In four children with hypoparathyroidism and deafness as initial major manifestations of Kearns-Sayre syndrome, a unique pattern of mitochondrial DNA rearrangements was observed. Hypocalcemic tetany caused by PTH deficiency started between age of 6-13 y and was well controlled by small amounts of 1.25-(OH)2-cholecalciferol. Rearranged mitochondrial genomes were present in blood cells of all patients and consisted of partially duplicated and deleted molecules, created by the loss of 7813, 8348, 8587, and 9485 bp, respectively. The deletions were localized between the origins of replication of heavy and light strands and encompassed at least eight polypeptide-encoding genes and six tRNA genes. Sequence analysis revealed imperfect direct repeats present in all rearrangements flanking the break-points. The duplicated population accounted for 25-53% of the mitochondrial genome and was predominant to the deleted DNA (5-30%) in all cases. The proportions of the mutant populations (30-75%) correlated with the age at onset of the disease. We conclude that, unlike heteroplasmic deletions, pleioplasmic rearrangements may escape selection in rapid-dividing cells, distribute widely over many tissues, and thus cause multisystem involvement. Hypoparathyroidism and deafness might be the result of altered signaling pathway caused by selective ATP deficiency.

Substituted dihydroxystilbenes 2 are suitable starting materials for the synthesis of photochromic systems derived from 3/4. Attempts to couple the naphthones 8a-8e by the McMurry reaction with TiCl3/LiAlH4 yielded mainly reduction products such as 8f, g or 9. However, the furofuran 3b was isolated when using the zinc–copper couple for reduction. The helicene 11 was formed as an unexpected by-product in the McMurry reaction of the pivaloylnaphthalene 8d.

By reaction of 1,4-naphthoquinone (1) and trialkylboranes in the presence of oxygen and oxidative work-up, sterically hindered 2-alkyl-1,4-naphthoquinones and, on addition of magnesium bromide, 2,3-bisalkyl-1,4-naphthoquinones are obtained

Thermochromic Furofuranes, II. — Synthesis and Thermolytic Behavior of Spiroquinole Ethers with Naphthalene Nucleus To obtain further insight into the new photochromic system 2/3, various 3,4-disubstituted spiroquinole ethers 7 have been synthesized by oxidation of 2-alkyl-4-methoxy-1-naphtholes 5 via the corresponding quinone methides 6. Unlike 7a, the ethers 7b–d did not yield dimeric quinone methides or furofuranes (type 2/3) on heating, but decomposed by retro-diene reaction yielding monomeric methides 6. The sterically hindered methides 6e, 6f are stable yellow compounds; 6c rearranged forming 12 which led to the naphthopyranes 11a/11b on further reaction with 6c.

We report on a method suitable for screening large regions (>3 kb) of mtDNA for structural changes of

By reaction of 1,4-naphthoquinone (1) and trialkylboranes in the presence of oxygen and oxidative work-up, sterically hindered 2-alkyl-1,4-naphthoquinones and, on addition of magnesium bromide, 2,3-bisalkyl-1,4-naphthoquinones are obtained