nal Aib CI3 atoms between a-helical alamethicin (AT, =250-290 ms, 298 K)[*'] and 12 (AT, =51 ms, 240 K) at comparable AS values (4.5 and 4.6 ppm, respectively) are strongly in favor of the 3,0-helix for 12. The exact eval- uation would require additional a-helical T1 data at 240 K. The energy barrier of the 3,,,-helix interconversion of 12 at T,=265 K (Fig. 3) could be estimated rather accurately by the coalescence method.['] The free energy of activation is AC' = 46 kJ mol - I , i. e., 4.6 kJ mol - per Aib residue. This value is much lower than the mean values determined for a-helices.

290 270 250 230 210 - TIKI

Fig. 3. Temperature dependence of the "C-NMR of 12 170 mg/0.5 m L CD2C12; internal standards CD2C12 (6= 53.8) and tert-butyl alcohol (rBu- OH) (6=30.0) at room temperature; 50 MHz, Bruker MSL 2001. In the insert, spectrum in the region of the Aib-C, signals at three temperatures: T=203 K, 6=21.4, 26.7, A6=5.3 ppm, frozen 310-helix interconversion; T,(T,,,)=265 K, broad coalescence signal (from which AGC=46 kJ mol- ' is derived): T=300 K, single Aib-C, signal at 6=25.1 due to fast 3',0*3;0 helix interconversion. The sharp signal at 6=28.0 corresponds to the methyl groups of the rerr-butyl ester protecting group (OrBu).

A corollary comparison between results from high-reso- lution and solid-state 13C-NMR spectroscopy (CPMAS) gave further support to our interpretation. The effect of freezing the 3',0"c3 i0 interconversion at very low tempera- ture was found to be comparable to that of shorter Aib ho- mopeptides in the solid state such as Z-(Aib),-OH (A6=2.5 ppm) and 2-(Aib),-OtBu (4.0 ppm). On the other hand, the Aib residues between the protein amino acid re- sidues in the conformationally more stable a-helices show A6 values of 3-5 ppm already in solution at room tempera- ture (Fig. 2).

The 3,,,-helix interconversion can be described as a fast monomolecular all-or-nothing process between enantio- meric P- and M-helical forms. A decision cannot be made

temperature. Inter aha, this could be one reason for the burstlike pore formation of trichotoxin in currentholtage experiments in lipid bilayer membranes," ' I in contrast to the stabile pore system of the a-helical and rigid alamethi- tin."] In addition, the surprising experimental results for this 3to-helix enantiotopomerization, which indicate, e. g., 1200 interconversions per second at room temperature for 12, appear to be of particular interest for conformational energy calculations.

Received: April 24, 1987 [Z 2220 IE] German version: Angew. Chem. 97(1987) 1180

[I] I. S . Richardson, Adu. Protein Chem. 34 (1981) 167. I21 a) E. Benedetti, A. Bavoso, B. Di Blasio, V. Pavone, C . Pedone, C. Ton-

iolo, G. M. Bonora, Proc. Narl. Acad. Sci. USA 79 (1982) 7951; b) H. Briickner, H. Graf, Experientio 39 (1983) 528.

[3] a) R. Bosch, G. Jung, H. Schmitt, G. M. Sheldrick, W. Winter, Angew. Chem. 96 (1984) 440; Angew. Chem. Inr. Ed. Engl. 23 (1984) 450, and references cited therein; b) C. Toniolo, G. M. Bonora, A. Bavoso, E. Benedetti, 8. Di Blasio, V. Pavone, C. Pedone, Biopolymers 22 (1983) 205; c) A. Bavoso, E. Benedetti, B. Di Blasio, V. Pavone, C. Pedone, C. Toniolo, G. M. Bonora, Proc. Natl. Acad. Sci. USA 83 (1986) 1988: d) B. V. Venkataram Prasad, P. Balaram, CRC Crir. Rev. Biochem. 16 (1984) 307; e) M. Kokkonidis, D. Tsernoglou, H. Briickner, Biochem Biophys. Res. Commun. 136 (1986) 870; f) B. R. Malcolm, M. D. Walkinshaw, Biopolymers 25 (1986) 607.

[4] a) R. D. Fox, Jr., F. M. Richards, Nature (London) 300 (1982) 325; b) R. Bosch, G. Jung, H. Schrnitt, W. Winter, Biopolymers 24 (1985) 961, 979: c) I . L. Karle, M. Sukumar, P. Balaram, Proc. Null. Acad. Sri. USA 83 (1986) 9284.

[ 5 ] G. Jung, R. Bosch, E. Katz, H. Schmitt, K.-P. Voges, W. Winter, Biopo- lymers 22 (1983) 241.

I61 a) K.-P. Voges, G. Jung, W. H. Sawyer, Biochim. Biophys. Acra 896 (1987) 64; b) G. Jung, N. Dubischar, D. Leibfritz, Eur J . Biochem. 54 (1975) 395; c) G. Esposito, J. A. Carver, J. Boyd, I . D. Campbell, Bio- chemisrry 26 (1987) 1043.

[7] a) G. Boheim, W. Hanke, G. Jung, Biophys. Strucr. Mech. 9 (1983) 181: b) G. Menestrina, K.-P. Voges, G. Jung, G. Boheim, J . Membr. Biol. 93 (1986) 111.

181 a) H. Schmitt. G. Jung, Liebigs Ann. Chem. 1985, 345; b) R. Bosch, G. Jung, K:P. Voges, W. Winter, ibid. 1984. I 117; c) G. Jung, H. Schmitt in U. Ragnarsson (Ed.), Peptides 1984. Almquist & Wiksell, Uppsala 1984, S . 569; d) the chiral 2-trideuteriomethylalanine (R)-[D,]Aib, which is particularly suitable for NMR studies, has been synthesized by T. Weih- rauch and D. Leibfriitz (Liebigs Ann. Chem. 1985. 1917), but not yet intro- duced into peptides.

191 a) H. Kessler, Angew. Chem. 82 (1970) 237; Angew. Chem. Int . Ed. Engl. 9 (1970) 219; b) G. Binsch, H. Kessler, ibid. 92 (1980) 445 and 19 (1980) 411.

[lo] C. Toniolo, G. M. Bonora, V. Barone, A. Bavoso, E. Benedetti, B. Di Blasio, G. Grimaldi, F. Lelj, V. Pavone, C. Pedone, Macromolecules 18 (1985) 895.

1111 W. Hanke, C. Methfessel, H.-U. Wilmsen, E. Katz, G. Jung, G. Boheim, Biochim. Biophys. Acra 727 (1983) 108.

A Novel Route to Cyclopentane Derivatives: A Radical Chain Reaction** By Klaus Weinges* and Wolfgang Sipos Dedicated to Professor Hermann Schildknecht on the occasion of his 65th birthday

Dienes whose double bonds exhibit variable reactivity because of substituent effects can undergo an intramolecu- lar cyclization when subjected to solvornercuration and subsequent reduction with complex boron or tin hy- d r i d e ~ . ~ ' - ~ ] We have now found that a mixture of the cyclo- pentane derivatives cis4a and trans-4a in the ratio 8 :2 is

so far whether measurable amounts of other conforma- 1'1 Prof. Dr. K. Weinges, DipLChem. W. Sipos tions exist at and above the melting temperature T,,, (= TJ. Our findings may be of relevance for short 310-helical seg-

Organisch-chemisches Institut der Universitat Im Neuenheimer Feld 270, D-6900 Heidelbere. 1 (FRG) - . ,

merits of peptaibols particularly rich in Aib, e.g., tricho- [**I This work was supported by the Land Baden-Wiirttemberg (FRG) (For- toxin,["l which could be conformationally labile at room

1152

schungsschwerpunkt No. 35).

0 VCH Verlagsgesells~ha$ mbH. 0-6940 Weinherm. 1987 0570-0833/87/1111-11SZ $ 02.50/0 Angew. Chem. In / . Ed. Engl. 26 (1987) No. 11

formed in 90% yield upon reaction of ethyl 8-methoxy-2,7- octadienoate 3 with mercury acetate in the presence of cal- cium oxide and methanol and subsequent reduction with NaBH, (Scheme 1).

CH=CH-CO2C2H5 b OH 5 6 -C C H X H OCHj

H = C H - C O Z C ~ ~

a,R=CH,OH, b,R=CHO

' ~

d.e 1 4a,R-C0,C2H, 5

b.R=CH,OH

Scheme I . a) (C,Hs)xP=CH-COIC2HS in DMF, 9 0 T , 12 h; 65% 2a. b) pyH"CICrO? in CH2Cl2, room temperature, 2 h ; 95% 2b. c) [(CSH5),P-CH20CH3]CI with tBuOK in T H F added dropwise to the solu- tion of 2b in THF, reflux, 1 h ; 68% 3. d) Hg(OAc)* and CaO in MeOH, room temperature, 2 h ; NaBH4, O"C, 5 min; 90% 4a. e) LiAlH4 in THF, reflux, I h ; 72% 4b. f ) 2 N HCI, extraction with ether; 70% 5 .

As starting material for the preparation of 3 we used the commercially available 2-hydroxytetrahydropyran 1, whose hemiacetal reacts with ethoxycarbonylmethylenetri- phenylphosphorane in a Wittig reaction to give 2a. Oxida- tion of the initially formed CH20H group of 2a with py- ridinium chlorochromate affords aldehyde 2b. Reaction of 2b with methoxymethylenetriphenylphosphorane in a sec- ond Wittig reaction affords 3 in good yield. Under identi- cal conditions optically active, C-3, C-4- or C-5-substituted 2-hydroxytetrahydropyrans furnish optically active, substi- tuted ethyl 8-methoxy-2,7-octadienoates. These are of spe- cial interest, since the chiral centers should influence the stereoselectivity of the subsequent cyclization.

Under the reaction conditions given for the cyclization in Scheme 1 the methanol attacks as intermolecular nu- cleophile during the mercuration step in such a way that the acetal 6 is formed (Scheme 2). Reaction of 6 with NaBH,, in accord with previous studies on intermolecular C-C affords the alkylmercury hydride 7, which is converted by loss of a hydrogen atom into the reactive alkylmercury radical 8. The radical 8 decomposes spontaneously into the carbon radical 9 and mercury. In- tramolecular C-C coupling in 9 leads to formation of 10. The function of the hydrogen donor, which traps the radi- cal 10 as 4a before a polymerization can take place, is as- sumed by the alkylmercury hydride 7. The reactive alkyl- mercury radical 8 is thereby set free and a radical chain

Hg@ t 8 9 I 10

Scheme 2. Mechanism of the radical chain reaction leading to the formation of 4a. R=CO2C2HS.

reaction takes place. It can be concluded from the 'H- NMR spectrum of 4a that the reaction proceeds with 80% cis-stereoselectivity.

The cyclization reaction is of interest for many reasons. The cis- 1 -hydroxyoctahydrocyclopenta[c]pyran 5 , which represents the basic carbon skeleton of the natural iridoids, can be obtained directly from 4a by LiAIH,-reduction of the ester group to give 4b, followed by acid hydrolysis in order to free the aldehyde group.I8] Accordingly, it should be possible to prepare enantiomerically pure iridoids from appropriate optically active starting compounds. Further- more, 4a contains already useful potentialities for the con- struction of a new diene by simple reactions. Further cycli- zations would then lead to polycyclopentanes, a class of compounds to which naturally occurring di- and triqui- nanes belong.[']

Received: June 19, 1987 [Z 2303 IE] German version: Angew. Chem. 99 (1987) 1177

CAS Registry numbers: 1, 694-54-2; 2a, 110935-49-4; 2b, 59612-36-1; 3, 110935-50-7; 4a (cis isomer), 110744-16-6; 4a (trans isomer), 110744-17-7; 4b, 110935-51-8; 5, 110744-18-8.

[ I ] Y. Matsuka, M. Kodarna, S . Ito, Tetrahedron Lett. 1979. 4081. 121 S . Danishefsky, S. Chakalamannil, B.-J. Uang, J . Org. Chem. 47 (1982)

[3] Review: B. Giese, Angew. Chern. 97 (1985) 555; Angew. Chem. lnt . Ed.

[4] G. M. Whitesides, J. San Filippo, J. Am. Chem. SOC. 92 (1970) 661 I . [5] C. L. Hill, G. M. Whitesides, J . Am. Chem. Soc. 96 (1974) 870. [6I M. Devaud, J . Organornet. Chem. 220 ( 1981) C27. [7] B. Giese, G. Kretzmar, Chem. Eer. 117 (1984) 3160. IS] Review: J. M. Bobbitt, K:P. Segebarth in A. R. Battersby, W. 1. Taylor

(Eds.): Cyclopenranoid Terpene Derrvatiues. Vol I . Dekker, New York 1969, p. 1.

2331.

Engl. 24 (1985) 553.

191 Review: L. A. Paquette, Top. Curr. Chem. 119 (1984) 84.

I(qs-CsMes)2Ti~P61, a Distorted Dimetallaphosphacubane** By Otto J . Scherer, * Herbert Swarowsky, Gotthelf Wolmershauser, Wolfgang Kaim. and Stephan Kohlmann

Conceptual replacement of the diagonally opposite corner atoms of the unknown cubic P, A"] by two transi- tion-metal complex fragments M gives the cubane-like M2Pb structure type B.

Cothermolysis of 1 and white phosphorus (P,) affords 2 in ca. 20% yield. Complex 2 was obtained in the form of red-brown crystals, which could be handled in the air and

[*] Prof. Dr. 0. J. Scherer, DipLChem. H. Swarowsky, Dr. G. Wolmershauser ['I Fachbereich Chemie der Universitat Erwin-Schrodinger-Strasse, D-6750 Kaiserslautern (FRG) Priv.-Doz. Dr. W. Kaim, DipLChem. S . Kohlmann lnstitut fur Anorganische Chemie der Universitat Niederurseler Hang, D-6000 Frankfurt am Main 50 (FRG)

1'1 X-ray structure analysis [**I This work was supported by the Fonds der Chemischen Industrie (doc-

toral fellowship for H.S.).

Angew Chem. Int . Ed. Engl. 26 (1987) No. I 1 0 VCH Verlagsgesellschafr rnbH. 0-6940 Weinheim. 1987 0570-0833/87/1111-1153 $ 02.50/0 1 153