An intramolecular Heck reaction (90 f 91) serves as the key step in the total synthesis of the titled compounds. The synthetic route is based on utilizing the Wieland-Miescher ketone (5) as a matrix to provide the C and D rings of the targets and to provide functionality implements for joining this sector to an A ring precursor (6). Catalytically induced enantiotopic control and early emplacement of the oxetane are other features of the route.

Nosiheptide (9671 R.P.) isolated from Streptomyces actuosus 40037 (NRRL 2954) is a sulfur-containing polypeptidic antibiotic, quite different from all the other members of this family. Very active in vitro against gram-positive bacteria, it is inactive in vivo in experimentally infected mice. Not toxic, even at high dose, it may be used as a feed additive for chickens and pigs and it shows a favourable effect on the growth and conversion index.

Time-resolved fluorescence anisotropy (FA) measurements are reported for five helical bilayer-spanning henicosapeptides, each containing one tryptophan at sequence position 1, 6, 11, 16, or 21. The FA decay reflects two molecular processes in all cases: local internal fluctuations of the tryptophan side chain with a relaxation time of 200-500 ps, and motions of the whole polypeptide molecule with a relaxation time of 9-10 ns. The amplitudes of the fast fluctuation are largest at the helix ends and decrease toward the center of the helix. A similar observation was made for the helical polypeptides dissolved in organic solvents showing that the mobility gradient along the polypeptide sequence is an inherent property of the polypeptide helix and not due to the lipid bilayer.However, the amplitudes of the fast fluctuations can be modulated by the physical state of the lipid bilayer. With decreasing temperature, the internal mobility of the tryptophan in all positions decreases with an abrupt change at the lipid-phase transition. Concomitant molecular dynamics calculations indicate a correlation between the fast FA decay and conformational fluctuations within the helix. According to the simulation, the conformation of the polypeptide is on average predominantly helical, but actually the molecule can fluctuate between a variety of different substructures. The conformational fluctuations are largest at the helix ends and provide the free space required for rotation of the indole ring around the tryptophan side chain bonds.A number of experimental and theoretical studies on watersoluble proteins indicated the presence of protein structural fluctuations that may play an essential role for biological activity (1-3). However, in the particular case of membrane proteins, little information exists concerning such structural fluctuations of a polypeptide in a lipid bilayer (4-6). Here we report on structural fluctuations of membrane-incorporated synthetic polypeptides of the type 'H2(Ala-Aib-Ala-AibAla),-Trp-(Ala-Aib-Ala-Aib-Ala)4_xOMe (Aib, a-aminoisobutyric acid) with x = 0, 1, 2, 3, 4-i.e., 21-amino-acid-long (henicosa) polypeptides, containing a tryptophan at sequence position 1,6,11,16,, , , , and ). A recent study (7) indicates that these polypeptides insert into lipid bilayers and traverse the membrane in an a-helical conformation. The tryptophan residue was found to be located near the membrane surface in and , around the center of the bilayer in (6,(8)(9)(10).These structural fluctuations are composed of internal motions of the tryptophan residue, that of the polypeptide backbone and the orientational fluctuations of the whole molecule in the lipid bilayer. The various kinds of motion are expected to occur on different time scales in a hierarchical order and, therefore, should be distinguished to a certain extent by timeresolved FA measurements. Using polypeptides with a tryptophan residue at different sequence positions, we can probe structural fluctuations along a polypeptide helix in a lipid bilayer. Ti...

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